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Search for "macrocyclic" in Full Text gives 266 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
BINOL as a chiral element in mechanically interlocked molecules
- Matthias Krajnc and
- Jochen Niemeyer
Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53
- . Accordingly, demetalation leads to an almost complete disappearance of the CD signals in this area (see Figure 2). Saito and coworkers demonstrated that the homochiral [2]rotaxane (R)-10 can be efficiently synthesized using an active metal template approach [44][45]. The macrocyclic phenanthroline (R)-7 was
- ) [59]. The catenane catalyst allows for the asymmetric transfer hydrogenation of 2-substituted quinolines by Hantzsch esters in a highly stereoselective fashion [60]. It was found that the catenated catalyst gives superior stereoselectivities in comparison to the macrocyclic and the acyclic reference
Graphical Abstract
Figure 1: Molecular structures of (R)-BINOL (left) and (S)-BINOL (right).
Figure 2: Synthesis of Sauvage´s [2]catenanes (S,S)-5 and (S,S)-6 containing two BINOL units by the passive m...
Figure 3: Synthesis of Saito´s [2]rotaxane (R)-10 from a BINOL-based macrocycle by the active metal template ...
Figure 4: Synthesis of Stoddart´s [2]rotaxane (rac)-14 by an ammonium crown ether template.
Figure 5: Synthesis of Stoddart´s BINOL-containing [2]catenanes 18/20/22/24 by π–π recognition.
Figure 6: Synthesis of Takata´s rotaxanes featuring chiral centers on the axle: a) rotaxane (R,R,R/S)-27 obta...
Figure 7: Takata´s chiral polyacetylenes 32/33 featuring BINOL-based [2]rotaxane side chains.
Figure 8: Synthesis of Takata´s chiral thiazolium [2]rotaxanes (R)-35a/b and (R)-38.
Figure 9: Results for the asymmetric benzoin condensation of benzaldehyde (39) with catalysts (R)-35a/b and (R...
Figure 10: Synthesis of Takata´s pyridine-based [2]rotaxane (R)-42.
Figure 11: The asymmetric desymmetrization reaction of meso-1,2-diols with rotaxane (R)-42.
Figure 12: Synthesis of Niemeyer´s axially chiral [2]catenane (S,S)-47.
Figure 13: Results for the enantioselective transfer hydrogenation of 2-phenylquinoline with catalysts (S,S)-47...
Figure 14: Synthesis of Niemeyer´s chiral [2]rotaxanes (S)-56/57.
Figure 15: Results for the enantioselective Michael addition with different rotaxane catalysts (S)-56a/56b/57a/...
Figure 16: Synthesis of Beer´s [2]rotaxanes 64a/b for anion recognition.
Figure 17: Association constants of different anions (used as the Bu4N+ salts) to the [2]rotaxanes (S)-64a/b a...
Figure 18: Synthesis of Beer´s [3]rotaxane (S)-68.
Figure 19: Association constants of different anions (used as the Bu4N+-salts) to the [2]rotaxane (S)-68 and a...
Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions
- Hao Guo,
- Yu-Fei Ao,
- De-Xian Wang and
- Qi-Qiang Wang
Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51
- readily incorporated by both homo and hetero [1 + 1] macrocyclic condensation of bisamine and bisisothiocyanate fragments. With the easy synthesis, gram-scale of macrocycle products can be readily obtained. These chiral macrocycles were applied in catalyzing bioinspired decarboxylative Mannich reactions
- . Only 5 mol % of the optimal macrocycle catalyst efficiently catalyzed the decarboxylative addition of a broad scope of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. The rigid macrocyclic framework and the cooperation between the thiourea and
- ][10][11][12][13][14]. Among which, macrocyclic compounds have attracted extensive attentions due to their enzyme-mimicking cavity and preorganized binding sites [4][6][15][16]. Various macrocyclic compounds including the privileged scaffolds like cyclodextrins [17][18][19], calixarenes [20][21][22][23
Graphical Abstract
Figure 1: Design of PKS-inspired multifunctional amino-thiourea macrocycle catalysts.
Scheme 1: Synthesis of tetraamino-bisthiourea chiral macrocycles M1–M12. The synthesis of M1, M5, M7, and M8 ...
Scheme 2: Substrate scope of isatin imines. Reaction conditions: 6 (0.2 mmol), 7a (0.3 mmol), and 5 mol % M3 ...
Scheme 3: Substrate scope of MAHTs. Reaction conditions: 6a (0.2 mmol), 7 (0.3 mmol), and 5 mol % M3 in 2 mL ...
Figure 2: Proposed catalytic mechanism.
Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water
- Zhihang Bai,
- Krishnasamy Velmurugan,
- Xueqi Tian,
- Minzan Zuo,
- Kaiya Wang and
- Xiao-Yu Hu
Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45
- to improve the efficiency of chemical reactions in water [26]. Until now, various macrocyclic host-assisted supramolecular donor–acceptor systems have been developed based on the FRET process and further utilized for different photochemical reactions [27][28]. For instance, Yi et al. [29] developed a
Graphical Abstract
Scheme 1:
Graphical representation of the fabrication of supramolecular m-TPEWP5![[Graphic 5]](/bjoc/content/inline/1860-5397-18-45-i7.svg?max-width=637&scale=1.18182)
G-EsY self-assembled photocat...
Figure 1: 1H NMR (400 MHz, D2O, 298 K) spectra of m-TPEWP5 (1.0 mM), m-TPEWP5 (1.0 mM) + G (1.0 mM), and G (1...
Figure 2: (a) Fluorescence spectra of m-TPEWP5 (1 × 10−5 M) with different concentrations of G (0 to 1.2 equi...
Figure 3:
TEM images of (a) m-TPEWP5![[Graphic 15]](/bjoc/content/inline/1860-5397-18-45-i17.svg?max-width=637&scale=1.18182)
G; (b) m-TPEWP5![[Graphic 16]](/bjoc/content/inline/1860-5397-18-45-i18.svg?max-width=637&scale=1.18182)
G-EsY. [m-TPEWP5] = 1 × 10−4 M, [G] = 1 × 10−4 M, [EsY] = ...
Figure 4:
(a) Normalized absorption and emission spectra of the EsY acceptor and the m-TPEWP5![[Graphic 25]](/bjoc/content/inline/1860-5397-18-45-i27.svg?max-width=637&scale=1.18182)
G donor assembly...
Scheme 2:
Products from 2-bromo-1-phenylethanone dehalogenation reactions in the presence of m-TPEWP5![[Graphic 43]](/bjoc/content/inline/1860-5397-18-45-i45.svg?max-width=637&scale=1.18182)
G-EsY na...
Figure 5:
Proposed mechanism for the 2-bromo-1-phenylethanone dehalogenation reaction mediated by m-TPEWP5![[Graphic 48]](/bjoc/content/inline/1860-5397-18-45-i50.svg?max-width=637&scale=1.18182)
G-E...
Diametric calix[6]arene-based phosphine gold(I) cavitands
- Gabriele Giovanardi,
- Andrea Secchi,
- Arturo Arduini and
- Gianpiero Cera
Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21
- macrocyclic cavity. Keywords: 1,2,3-alternate conformation; calix[6]arenes; gold(I) catalysis; phosphines; Introduction One of the latest challenges in supramolecular chemistry is the design and development of novel macrocyclic-based entities able to influence the catalytic activities of the metal center [1
- catalytic activity was demonstrated in promoting gold(I)-catalyzed cycloisomerization of 1,6-enynes, with ample scope and high regioselectivity. However, preliminary studies suggested that the catalytic event occurs outside the macrocyclic cavity. In order to get more insights on the role of the cavity to
- gold(I) nuclei to the opposite sides of the macrocycle, offering them the possibility to approach the cavity, thus exerting any control over the catalytic manifold (Figure 1d). Results and Discussion Synthesis and characterization The synthesis of novel macrocyclic calix[6]arene ligands was first
Graphical Abstract
Figure 1: Selected examples of: a) calix[4]arene-; b) resorcin[4]arene-; c) calix[6]arene-gold(I) macrocyclic...
Scheme 1: i) NH2NH2∙H2O, Pd/C in EtOH, 80 °C (quant.); ii) diphenylphosphinobenzoic acid, EDC∙HCl, DMAP (cat....
Figure 2: Stacked-plot, mid-field expanded region of the 1H NMR spectrum (400 MHz, 298 K) of A(AuCl)2, B(AuCl)...
Figure 3: Stacked plot 1H NMR (tetrachloroethane-d2) of A(AuCl)2 at variable temperature.
Scheme 2: Synthesis of the monomeric gold catalyst analogues A’,B’,C’(AuCl). Conditions: i) diphenylphosphino...
Synthesis and late stage modifications of Cyl derivatives
- Phil Servatius and
- Uli Kazmaier
Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19
- metabolites for self-defense in different microorganisms, peptidic natural products are assembled either by ribosomal synthesis or by non-ribosomal peptide synthetases (NRPS) [2]. Macrocyclic peptides are pervasive throughout this class of natural products and often show improved stability against proteolytic
- interactions with residues on the rim of the active site [15]. The cap region of acyclic HDAC inhibitors is generally small, resulting in non-specific interactions with the different HDAC isoforms. More diverse cap regions are found in macrocyclic HDAC inhibitors such as trapoxin which contains the unusual
Graphical Abstract
Figure 1: Naturally occurring HDAC inhibitors.
Figure 2: Naturally occurring HDAC inhibitors with different zinc-binding motifs.
Scheme 1: Planned syntheses of Cyl-1 derivatives.
Scheme 2: Cyl-1 derivatives via peptide Claisen rearrangement.
Scheme 3: Synthesis of tetrapeptide allyl esters 8.
Scheme 4: Synthesis and late stage modifications of Cyl derivatives.
Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum
- Yasuhiro Igarashi,
- Yiwei Ge,
- Tao Zhou,
- Amit Raj Sharma,
- Enjuro Harunari,
- Naoya Oku and
- Agus Trianto
Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12
- produced by both Gram-positive and -negative bacteria and have a linear or macrocyclic backbone [23][30] composed of alternately arranged cadaverine or putrescine and succinic acid modules with N-hydroxylation at every other amide bond. Modifications of these core structures include internal hydroxylation
Graphical Abstract
Figure 1: Structures of tenacibactins K–M (1–3).
Figure 2: Key 2D-NMR correlations for 1–3.
Figure 3: (a) Partial 1H NMR spectra of 1 at 25 and 50 °C in DMSO-d6; (b) magnified HMBC spectrum of 1 at 25 ...
Figure 4: MS/MS spectrum of 1 acquired on a quadrupole time-of-flight mass spectrometer in the negative ion m...
Scheme 1: MS/MS fragmentation pathway for compound 1.
Peptide stapling by late-stage Suzuki–Miyaura cross-coupling
- Hendrik Gruß,
- Rebecca C. Feiner,
- Ridhiwan Mseya,
- David C. Schröder,
- Michał Jewgiński,
- Kristian M. Müller,
- Rafał Latajka,
- Antoine Marion and
- Norbert Sewald
Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1
- diastereomers, i.e. cis/trans isomers or conformers with a high interconversion barrier. For complestatin-based macrocyclic peptides, the existence of biaryl atropisomers caused by the indole of tryptophan has been reported [82]. Recently, the occurrence of isomers was also observed in our group for SMC
Graphical Abstract
Scheme 1: Synthesis of SMC stapled axin CBD peptides. Reaction conditions: (a) Pd2(dba)3, sSPhos, KF, DME/EtO...
Scheme 2: Overview of the different cross-linkages obtained by intramolecular SMC. A) General structure of SM...
Figure 1: Analysis of the secondary structure by circular dichroism: CD spectra of both isomers of stapled pe...
Figure 2: In vitro binding affinities to β-catenin determined by competitive fluorescence polarisation assays....
Figure 3: Cleavage sites of Proteinase K digestion indicated by a red arrow.
Figure 4: Principal component analysis (PCA) of the macrocycle’s non-hydrogen atoms in the two isomers of P5....
Figure 5: Molecular modelling of the conformational preferences of the SMC stapled peptides P5 (with cis or t...
Study on the interactions between melamine-cored Schiff bases with cucurbit[n]urils of different sizes and its application in detecting silver ions
- Jun-Xian Gou,
- Yang Luo,
- Xi-Nan Yang,
- Wei Zhang,
- Ji-Hong Lu,
- Zhu Tao and
- Xin Xiao
Beilstein J. Org. Chem. 2021, 17, 2950–2958, doi:10.3762/bjoc.17.204
- Jun-Xian Gou Yang Luo Xi-Nan Yang Wei Zhang Ji-Hong Lu Zhu Tao Xin Xiao Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China 10.3762/bjoc.17.204 Abstract Three different complexes, TMeQ[6]-TBT, Q[7]-TBT, and Q[8]-TBT are
Graphical Abstract
Scheme 1: The Structures of Q[7], Q[8], TMeQ[6], and TBT.
Figure 1: The 1H NMR titration of TBT (1 mM) with an increasing amount of TMeQ[6] from 0 (i), 0.1 (ii), 0.2 (...
Figure 2: The 1H NMR titration of TBT (1 mM) with an increasing amount of Q[7] from 0 (i), 0.1 (ii), 0.5 (iii...
Figure 3: The UV–vis spectra (a) of TBT (20 μM) with an increasing amount of Q[7] from 0.0 to 4.0 equiv; the ...
Figure 4: The UV–vis spectra (a) of TBT (20 μM) with an increasing amount of Q[8] from 0.0 to 4.0 equiv and t...
Figure 5: The UV–vis spectra (a) of Q[7]-TBT (3:1, 20 μM) affected by Mn+ (50 equivalents); histogram of (b) ...
Figure 6: The UV–vis spectra (a) of Q[7]-TBT (20 μM) with an increasing amount of Ag+ from 0.0 to 2.0 equiv; ...
Scheme 2: The synthesis of TBT.
Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions
- Qingkai Zeng,
- Qiumeng Long,
- Jihong Lu,
- Li Wang,
- Yuting You,
- Xiaoting Yuan,
- Qianjun Zhang,
- Qingmei Ge,
- Hang Cong and
- Mao Liu
Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195
- Macrocycles with converging binding sites and functional groups hold a key position in supramolecular chemistry, which has been repeatedly confirmed by classic macrocyclic molecules, such as crown ethers, cyclodextrins, calixarenes, cucurbiturils and their homologues [1]. For the past decades, numerous
- initially studied. Among the metal cations examined, the fluorescence intensity of macrocycle 4 quenched significantly when adding the corresponding equivalents of Fe3+ and Cu2+. Notably, this macrocyclic host molecule formed 1:1 complexes with Fe3+ in DMF with an association constant up to (2.1 ± 0.3
- % yield and 30.0% yield based on starting compounds 5 and 6, respectively (Scheme 2). With the trimers 7 and 8 in hand, the reaction conditions for the [3 + 3] macrocyclic condensation were examined. Due to the low solubility of compound 7, the subsequent reactions were conducted in DMF. With two
Graphical Abstract
Scheme 1: The evolution of hemicucurbituril analogs.
Scheme 2: The route for the synthesis of aminobenzene-containing hemicucurbituril 4.
Figure 1: The X-ray structure of nitrobenzene-containing hemicucurbituril 9 (CCDC 2094879).
Figure 2: Fluorescence emission spectra (λmax = 349 nm) of 4 (2.5 × 10−5 M) in the presence of 10 equivalents...
Figure 3: Column diagram of fluorescence quenching efficiency of 4 (2.5 × 10−5 M) in the presence of 10 equiv...
Figure 4: Fluorescence emission spectra (λmax = 349 nm) of 4 (2.5 × 10−5 M) in the presence of Fe3+ and Cu2+ ...
Figure 5: Fluorescence emission spectra (λmax = 349 nm) of 4 (2.5 × 10−5 M) in the presence of 20 equivalents...
Figure 6: Column diagram of fluorescence enhancement efficiency of 4 (2.5 × 10−5 M) in the presence of 20 equ...
Host–guest interaction and properties of cucurbit[8]uril with chloramphenicol
- Lin Zhang,
- Jun Zheng,
- Guangyan Luo,
- Xiaoyue Li,
- Yunqian Zhang,
- Zhu Tao and
- Qianjun Zhang
Beilstein J. Org. Chem. 2021, 17, 2832–2839, doi:10.3762/bjoc.17.194
- Lin Zhang Jun Zheng Guangyan Luo Xiaoyue Li Yunqian Zhang Zhu Tao Qianjun Zhang Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China 10.3762/bjoc.17.194 Abstract The interaction between cucurbit[8]uril (Q[8]) and chloramphenicol
Graphical Abstract
Figure 1: The structures of chloramphenicol (A) and cucurbit[n]urils (B).
Figure 2: (A) CPE and Q[8] structural model diagram, (B) interaction between CPE and Q[8], (C) CPE@Q[8] stack...
Figure 3: UV–vis absorption spectra of CPE with Q[8] in aqueous solution (A) or hydrochloric acid solution (C...
Figure 4: ITC data obtained for the binding of Q[8] with CPE in an aqueous solution at 25 °C.
Figure 5: 1H NMR spectra of CPE, CPE@Q[8] and Q[8] (VD2O/VDCl = 3:2).
Figure 6: IR spectra recorded for Q[8] (a), CPE (b), a physical mixture of Q[8] and CPE (c), and the CPE@Q[8]...
Figure 7: UV absorption intensity of CPE and CPE@Q[8] changes with time in the artificial gastrointestinal ju...
Figure 8: Release curve of CPE and CPE@Q[8] in artificial gastrointestinal juice (pH 1.2, pH 6.8).
The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids
- Marco Keller,
- Karl Sauvageot-Witzku,
- Franz Geisslinger,
- Nicole Urban,
- Michael Schaefer,
- Karin Bartel and
- Franz Bracher
Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183
- . Interestingly, macrocyclic bisbenzylisoquinolines such as tetrandrine [48][49] and related alkaloids [50], have been reported to inhibit P‐glycoprotein (P-gp), a crucial factor of multidrug resistance in cancer. This is noteworthy as multidrug resistance is still a major problem in cancer therapy and no
Graphical Abstract
Figure 1: Prominent synthetic approaches to 1-benzyltetrahydroisoquinolines: Bischler–Napieralski, Pictet–Spe...
Figure 2: Structures of N-methylcoclaurine (1) and the ten 1-benzyl-1,2,3,4-tetrahydroisoquinoline alkaloids ...
Figure 3: Two routes using N- and O-alkoxycarbonylated building blocks for the synthesis of phenolic N-methyl...
Figure 4: Structures of the building blocks A1–A4 (N-ethoxycarbonyl phenethylamines) and B1–B3 (ω-methoxystyr...
Figure 5: Biological activity. Antiproliferative effects of the 1-benzyltetrahydroisoquinoline alkaloids in A...
Halides as versatile anions in asymmetric anion-binding organocatalysis
- Lukas Schifferer,
- Martin Stinglhamer,
- Kirandeep Kaur and
- Olga García Macheño
Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145
- , respectively. Bis- and macrocyclic thiourea catalysts Besides the introduction of cation–π interactions in anion-binding catalyst design, bisthiourea catalysts have been applied with the aim of accelerating certain catalytic reactions. In this regard, the group of Seidel reported in 2016 an enantioselective
- aromatic aldehydes under weakly acidic conditions. Anion-binding catalyst development in the enantioselective addition of silyl ketene acetals to 1-chloroisochromane (73). Limiting factors and influences on catalyst activation and anion abstraction. a) Macrocyclic bis-thiourea catalyst in a
Graphical Abstract
Figure 1: a) Binding interactions in the chloride channel of E. coli. and b) examples of chloride, cyanide, n...
Figure 2: a) H-bond vs anion-binding catalysis and b) activation modes in anion-binding catalysis.
Scheme 1: First proposed anion-binding mechanism in the thiourea-catalyzed acetalization of benzaldehyde.
Scheme 2: a) Thiourea-catalyzed enantioselective acyl-Pictet–Spengler reaction of tryptamine-derived imines 4...
Scheme 3: Proposed mechanism of the thiourea-catalyzed enantioselective Pictet–Spengler reaction of hydroxyla...
Scheme 4: a) Thiourea-catalyzed intramolecular Pictet–Spengler-type cyclization of hydroxylactam-derived N-ac...
Scheme 5: Enantioselective Reissert-type reactions of a) (iso)quinolines with silyl ketene acetals, and b) vi...
Figure 3: Role of the counter-anion: a) Anion acting as a spectator and b) anion participating directly as th...
Scheme 6: Enantioselective selenocyclization catalyzed by squaramide 28.
Scheme 7: Desymmetrization of meso-aziridines catalyzed by bifunctional thiourea catalyst 31.
Scheme 8: Anion-binding-catalyzed desymmetrization of a) meso-aziridines catalyzed by chiral triazolium catal...
Scheme 9: Bis-urea-catalyzed enantioselective fluorination of a) β-bromosulfides and b) β-haloamines by Gouve...
Scheme 10: a) Bifunctional thiourea anion-binding – basic/nucleophilic catalysts. Selected applications in b) ...
Scheme 11: Thiourea-catalyzed enantioselective polycyclization reaction of hydroxylactams 51 through cation–π ...
Scheme 12: Enantioselective aza-Sakurai cyclization of hydroxylactams 56 implicating additional cation–π and L...
Scheme 13: Enantioselective tail-to-head cyclization of neryl chloride derivatives.
Scheme 14: Cation–π interactions in anion binding-catalyzed asymmetric addition reactions: a) addition of indo...
Scheme 15: Bisthiourea catalyzed oxa-Pictet–Spengler reaction of indole-based alcohols and aromatic aldehydes ...
Scheme 16: Anion-binding catalyst development in the enantioselective addition of silyl ketene acetals to 1-ch...
Scheme 17: a) Macrocyclic bis-thiourea catalyst in a diastereoselective glycosylation reaction. b) Competing SN...
Scheme 18: a) Folding mechanism of oligotriazoles upon anion recognition. b) Representative tetratriazole 82 c...
Scheme 19: Switchable chiral tetratriazole catalyst 86 in the enantioselective addition of silyl ketene acetal...
Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura
- Zhiwei Zhang,
- Tao Zhou,
- Taehui Yang,
- Keisuke Fukaya,
- Enjuro Harunari,
- Shun Saito,
- Katsuhisa Yamada,
- Chiaki Imada,
- Daisuke Urabe and
- Yasuhiro Igarashi
Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141
- with a known congener, nomimicin A (4), from Actinomadura sp. AKA43. Compounds 1 and 2 are new members of the spirotetronate-class antibiotics, characterized by a macrocyclic structure containing a trans-decalin unit and a tetronic acid moiety spiro-linked with a cyclohexene ring. To date, more than
- 100 compounds [21][22], including tetrocarcin [23] and kijanimicin [24], are known within the spirotetronate class. Of these, nomimicins A–C (4, 1, and 2) are featured by the smallest macrocyclic ring and highly oxygenated dehydrodecalin moiety. Spirotetronates are known to be constructed by the
Graphical Abstract
Figure 1: Structures of nomimicins A–D (4 and 1–3).
Figure 2: COSY and key HMBC correlations for 1.
Figure 3: Relative configuration of 1 determined by ROESY analysis.
Figure 4: Experimental ECD spectra of 1, 2, and 4 and calculated ECD spectrum of 4.
Figure 5: Four tautomers 4a–4d of the tetronic acid moiety of 4 and calculated ECD spectra.
Figure 6: COSY and key HMBC correlations for 3.
Figure 7: Relative configuration of 3 determined by NOESY analysis.
Progress and challenges in the synthesis of sequence controlled polysaccharides
- Giulio Fittolani,
- Theodore Tyrikos-Ergas,
- Denisa Vargová,
- Manishkumar A. Chaube and
- Martina Delbianco
Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129
- )-glucosamine macrocyclic compounds [265]. The iterative glycosylation of N-Phth protected 2-deoxy-2-aminothioglycosides allowed for the combinatorial synthesis of short oligoglucosamines having β(1–6) and/or β(1–4)-linkages [263]. Automated solution-phase synthesis of β(1–6)-glucosamine oligosaccharides
Graphical Abstract
Figure 1: Overview of the methods available for the synthesis of polysaccharides. For each method, advantages...
Figure 2: Overview of the classes of polysaccharides discussed in this review. Each section deals with polysa...
Scheme 1: Enzymatic and chemical polymerization approaches provide cellulose oligomers with a non-uniform dis...
Scheme 2: AGA of a collection of cellulose analogues obtained using BBs 6–9. Specifically placed modification...
Figure 3: Chemical structure of the different branches G, X, L, F commonly found in XGs. Names are given foll...
Scheme 3: AGA of XG analogues with defined side chains. The AGA cycle includes coupling (TMSOTf), Fmoc deprot...
Figure 4: Synthetic strategies and issues associated to the formation of the β(1–3) linkage.
Scheme 4: Convergent synthesis of β(1–3)-glucans using a regioselective glycosylation strategy.
Scheme 5: DMF-mediated 1,2-cis glycosylation. A) General mechanism and B) examples of α-glucans prepared usin...
Scheme 6: Synergistic glycosylation strategy employing a nucleophilic modulation strategy (TMSI and Ph3PO) in...
Scheme 7: Different approaches to produce xylans. A) Polymerization techniques including ROP, and B) enzymati...
Scheme 8: A) Synthesis of arabinofuranosyl-decorated xylan oligosaccharides using AGA. Representative compoun...
Scheme 9: Chemoenzymatic synthesis of COS utilizing a lysozyme-catalyzed transglycosylation reaction followed...
Scheme 10: Synthesis of COS using an orthogonal glycosylation strategy based on the use of two different LGs.
Scheme 11: Orthogonal N-PGs permitted the synthesis of COS with different PA.
Scheme 12: AGA of well-defined COS with different PA using two orthogonally protected BBs. The AGA cycle inclu...
Scheme 13: A) AGA of β(1–6)-N-acetylglucosamine hexasaccharide and dodecasaccharide. AGA includes cycles of co...
Figure 5: ‘Double-faced’ chemistry exemplified for ᴅ-Man and ʟ-Rha. Constructing β-Man linkages is considerab...
Figure 6: Implementation of a capping step after each glycosylation cycle for the AGA of a 50mer oligomannosi...
Scheme 14: AGA enabled the synthesis of a linear α(1–6)-mannoside 100mer 93 within 188 h and with an average s...
Scheme 15: The 151mer branched polymannoside was synthesized by a [30 + 30 + 30 + 30 + 31] fragment coupling. ...
Figure 7: PG stereocontrol strategy to obtain β-mannosides. A) The mechanism of the β-mannosylation reaction ...
Scheme 16: A) Mechanism of 1,2-cis stereoselective glycosylation using ManA donors. Once the ManA donor is act...
Figure 8: A) The preferred 4H3 conformation of the gulosyl oxocarbenium ion favors the attack of the alcohol ...
Scheme 17: AGA of type I rhamnans up to 16mer using disaccharide BB 115 and CNPiv PG. The AGA cycle includes c...
Figure 9: Key BBs for the synthesis of the O-antigen of Bacteroides vulgatus up to a 128mer (A) and the CPS o...
Figure 10: Examples of type I and type II galactans synthesized to date.
Figure 11: A) The DTBS PG stabilizes the 3H4 conformation of the Gal oxocarbenium ion favoring the attack of t...
Figure 12: Homogalacturonan oligosaccharides synthesized to date. Access to different patterns of methyl-ester...
Figure 13: GlfT2 from Mycobacterium tuberculosis catalyzes the sequential addition of UPD-Galf donor to a grow...
Figure 14: The poor reactivity of acceptor 137 hindered a stepwise synthesis of the linear galactan backbone a...
Scheme 18: AGA of a linear β(1–5) and β(1–6)-linked galactan 20mer. The AGA cycle includes coupling (NIS/TfOH)...
Figure 15: The 92mer arabinogalactan was synthesized using a [31 + 31 + 30] fragment coupling between a 31mer ...
Scheme 19: Synthesis of the branched arabinofuranose fragment using a six component one-pot synthesis. i) TTBP...
Figure 16: A) Chemical structure and SNFG of the representative disaccharide units forming the GAG backbones, ...
Figure 17: Synthetic challenges associated to the H/HS synthesis.
Scheme 20: Degradation of natural heparin and heparosan generated valuable disaccharides 150 and 151 that can ...
Scheme 21: A) The one-step conversion of cyanohydrin 156 to ʟ-iduronamide 157 represent the key step for the s...
Scheme 22: A) Chemoenzymatic synthesis of heparin structures, using different types of UDP activated natural a...
Scheme 23: Synthesis of the longest synthetic CS chain 181 (24mer) using donor 179 and acceptor 180 in an iter...
Scheme 24: AGA of a collection of HA with different lengths. The AGA cycle includes coupling (TfOH) and Lev de...
On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets
- Renato L. Carvalho,
- Amanda S. de Miranda,
- Mateus P. Nunes,
- Roberto S. Gomes,
- Guilherme A. M. Jardim and
- Eufrânio N. da Silva Júnior
Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126
- , several products were submitted to a subsequent metathesis mediated by Grubbs-II catalyst and a further palladium-catalyzed C=C reduction and DG-removal process, from which the desired macrocyclic peptides were obtained in good to excellent yields (Scheme 35C). Recently, again Ackermann and co-workers
Graphical Abstract
Scheme 1: Schematic overview of transition metals studied in C–H activation processes.
Scheme 2: (A) Known biological activities related to benzimidazole-based compounds; (B and C) an example of a...
Scheme 3: (A) Known biological activities related to quinoline-based compounds; (B and C) an example of a sca...
Scheme 4: (A) Known biological activities related to sulfur-containing compounds; (B and C) an example of a s...
Scheme 5: (A) Known biological activities related to aminoindane derivatives; (B and C) an example of a scand...
Scheme 6: (A) Known biological activities related to norbornane derivatives; (B and C) an example of a scandi...
Scheme 7: (A) Known biological activities related to aniline derivatives; (B and C) an example of a titanium-...
Scheme 8: (A) Known biological activities related to cyclohexylamine derivatives; (B) an example of an intram...
Scheme 9: (A) Known biologically active benzophenone derivatives; (B and C) photocatalytic oxidation of benzy...
Scheme 10: (A) Known bioactive fluorine-containing compounds; (B and C) vanadium-mediated C(sp3)–H fluorinatio...
Scheme 11: (A) Known biologically active Lythraceae alkaloids; (B) synthesis of (±)-decinine (30).
Scheme 12: (A) Synthesis of (R)- and (S)-boehmeriasin (31); (B) synthesis of phenanthroindolizidines by vanadi...
Scheme 13: (A) Known bioactive BINOL derivatives; (B and C) vanadium-mediated oxidative coupling of 2-naphthol...
Scheme 14: (A) Known antiplasmodial imidazopyridazines; (B) practical synthesis of 41.
Scheme 15: (A) Gold-catalyzed drug-release mechanism using 2-alkynylbenzamides; (B and C) chromium-mediated al...
Scheme 16: (A) Examples of anti-inflammatory benzaldehyde derivatives; (B and C) chromium-mediated difunctiona...
Scheme 17: (A and B) Manganese-catalyzed chemoselective intramolecular C(sp3)–H amination; (C) late-stage modi...
Scheme 18: (A and B) Manganese-catalyzed C(sp3)–H amination; (C) late-stage modification of a leelamine deriva...
Scheme 19: (A) Known bioactive compounds containing substituted N-heterocycles; (B and C) manganese-catalyzed ...
Scheme 20: (A) Known indoles that present GPR40 full agonist activity; (B and C) manganese-catalyzed C–H alkyl...
Scheme 21: (A) Examples of known biaryl-containing drugs; (B and C) manganese-catalyzed C–H arylation through ...
Scheme 22: (A) Known zidovudine derivatives with potent anti-HIV properties; (B and C) manganese-catalyzed C–H...
Scheme 23: (A and B) Manganese-catalyzed C–H organic photo-electrosynthesis; (C) late-stage modification.
Scheme 24: (A) Example of a known antibacterial silylated dendrimer; (B and C) manganese-catalyzed C–H silylat...
Scheme 25: (A and B) Fe-based small molecule catalyst applied for selective aliphatic C–H oxidations; (C) late...
Scheme 26: (A) Examples of naturally occurring gracilioethers; (B) the first total synthesis of gracilioether ...
Scheme 27: (A and B) Selective aliphatic C–H oxidation of amino acids; (C) late-stage modification of proline-...
Scheme 28: (A) Examples of Illicium sesquiterpenes; (B) first chemical synthesis of (+)-pseudoanisatin (80) in...
Scheme 29: (A and B) Fe-catalyzed deuteration; (C) late-stage modification of pharmaceuticals.
Scheme 30: (A and B) Biomimetic Fe-catalyzed aerobic oxidation of methylarenes to benzaldehydes (PMHS, polymet...
Scheme 31: (A) Known tetrahydroquinolines with potential biological activities; (B and C) redox-selective Fe c...
Scheme 32: (A) Known drugs containing a benzofuran unit; (B and C) Fe/Cu-catalyzed tandem O-arylation to acces...
Scheme 33: (A) Known azaindolines that act as M4 muscarinic acetylcholine receptor agonists; (B and C) intramo...
Scheme 34: (A) Known indolinones with anticholinesterase activity; (B and C) oxidative C(sp3)–H cross coupling...
Scheme 35: (A and B) Cobalt-catalyzed C–H alkenylation of C-3-peptide-containing indoles; (C) derivatization b...
Scheme 36: (A) Cobalt-Cp*-catalyzed C–H methylation of known drugs; (B and C) scope of the o-methylated deriva...
Scheme 37: (A) Known lasalocid A analogues; (B and C) three-component cobalt-catalyzed C–H bond addition; (D) ...
Scheme 38: (A and B) Cobalt-catalyzed C(sp2)–H amidation of thiostrepton.
Scheme 39: (A) Known 4H-benzo[d][1,3]oxazin-4-one derivatives with hypolipidemic activity; (B and C) cobalt-ca...
Scheme 40: (A and B) Cobalt-catalyzed C–H arylation of pyrrole derivatives; (C) application for the synthesis ...
Scheme 41: (A) Known 2-phenoxypyridine derivatives with potent herbicidal activity; (B and C) cobalt-catalyzed...
Scheme 42: (A) Natural cinnamic acid derivatives; (B and C) cobalt-catalyzed C–H carboxylation of terminal alk...
Scheme 43: (A and B) Cobalt-catalyzed C–H borylation; (C) application to the synthesis of flurbiprofen.
Scheme 44: (A) Benzothiazoles known to present anticonvulsant activities; (B and C) cobalt/ruthenium-catalyzed...
Scheme 45: (A and B) Cobalt-catalyzed oxygenation of methylene groups towards ketone synthesis; (C) synthesis ...
Scheme 46: (A) Known anticancer tetralone derivatives; (B and C) cobalt-catalyzed C–H difluoroalkylation of ar...
Scheme 47: (A and B) Cobalt-catalyzed C–H thiolation; (C) application in the synthesis of quetiapine (153).
Scheme 48: (A) Known benzoxazole derivatives with anticancer, antifungal, and antibacterial activities; (B and...
Scheme 49: (A and B) Cobalt-catalyzed C–H carbonylation of naphthylamides; (C) BET inhibitors 158 and 159 tota...
Scheme 50: (A) Known bioactive pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives; (B and C) cobalt-catalyzed C–H ...
Scheme 51: (A) Known antibacterial cyclic sulfonamides; (B and C) cobalt-catalyzed C–H amination of propargyli...
Scheme 52: (A and B) Cobalt-catalyzed intramolecular 1,5-C(sp3)–H amination; (C) late-stage functionalization ...
Scheme 53: (A and B) Cobalt-catalyzed C–H/C–H cross-coupling between benzamides and oximes; (C) late-state syn...
Scheme 54: (A) Known anticancer natural isoquinoline derivatives; (B and C) cobalt-catalyzed C(sp2)–H annulati...
Scheme 55: (A) Enantioselective intramolecular nickel-catalyzed C–H activation; (B) bioactive obtained motifs;...
Scheme 56: (A and B) Nickel-catalyzed α-C(sp3)–H arylation of ketones; (C) application of the method using kno...
Scheme 57: (A and B) Nickel-catalyzed C(sp3)–H acylation of pyrrolidine derivatives; (C) exploring the use of ...
Scheme 58: (A) Nickel-catalyzed C(sp3)–H arylation of dioxolane; (B) library of products obtained from biologi...
Scheme 59: (A) Intramolecular enantioselective nickel-catalyzed C–H cycloalkylation; (B) product examples, inc...
Scheme 60: (A and B) Nickel-catalyzed C–H deoxy-arylation of azole derivatives; (C) late-stage functionalizati...
Scheme 61: (A and B) Nickel-catalyzed decarbonylative C–H arylation of azole derivatives; (C) application of t...
Scheme 62: (A and B) Another important example of nickel-catalyzed C–H arylation of azole derivatives; (C) app...
Scheme 63: (A and B) Another notable example of a nickel-catalyzed C–H arylation of azole derivatives; (C) lat...
Scheme 64: (A and B) Nickel-based metalorganic framework (MOF-74-Ni)-catalyzed C–H arylation of azole derivati...
Scheme 65: (A) Known commercially available benzothiophene-based drugs; (B and C) nickel-catalyzed C–H arylati...
Scheme 66: (A) Known natural tetrahydrofuran-containing substances; (B and C) nickel-catalyzed photoredox C(sp3...
Scheme 67: (A and B) Another notable example of a nickel-catalyzed photoredox C(sp3)–H alkylation/arylation; (...
Scheme 68: (A) Electrochemical/nickel-catalyzed C–H alkoxylation; (B) achieved scope, including three using na...
Scheme 69: (A) Enantioselective photoredox/nickel catalyzed C(sp3)–H arylation; (B) achieved scope, including ...
Scheme 70: (A) Known commercially available trifluoromethylated drugs; (B and C) nickel-catalyzed C–H trifluor...
Scheme 71: (A and B) Stereoselective nickel-catalyzed C–H difluoroalkylation; (C) late-stage functionalization...
Scheme 72: (A) Cu-mediated ortho-amination of oxalamides; (B) achieved scope, including derivatives obtained f...
Scheme 73: (A) Electro-oxidative copper-mediated amination of 8-aminoquinoline-derived amides; (B) achieved sc...
Scheme 74: (A and B) Cu(I)-mediated C–H amination with oximes; (C) derivatization using telmisartan (241) as s...
Scheme 75: (A and B) Cu-mediated amination of aryl amides using ammonia; (C) late-stage modification of proben...
Scheme 76: (A and B) Synthesis of purine nucleoside analogues using copper-mediated C(sp2)–H activation.
Scheme 77: (A) Copper-mediated annulation of acrylamide; (B) achieved scope, including the synthesis of the co...
Scheme 78: (A) Known bioactive compounds containing a naphthyl aryl ether motif; (B and C) copper-mediated eth...
Scheme 79: (A and B) Cu-mediated alkylation of N-oxide-heteroarenes; (C) late-stage modification.
Scheme 80: (A) Cu-mediated cross-dehydrogenative coupling of polyfluoroarenes and alkanes; (B) scope from know...
Scheme 81: (A) Known anticancer acrylonitrile compounds; (B and C) Copper-mediated cyanation of unactivated al...
Scheme 82: (A) Cu-mediated radiofluorination of 8-aminoquinoline-derived aryl amides; (B) achieved scope, incl...
Scheme 83: (A) Examples of natural β-carbolines; (B and C) an example of a zinc-catalyzed C–H functionalizatio...
Scheme 84: (A) Examples of anticancer α-aminophosphonic acid derivatives; (B and C) an example of a zinc-catal...
A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries
- Guido Gambacorta,
- James S. Sharley and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
Structural effects of meso-halogenation on porphyrins
- Keith J. Flanagan,
- Maximilian Paradiz Dominguez,
- Zoi Melissari,
- Hans-Georg Eckhardt,
- René M. Williams,
- Dáire Gibbons,
- Caroline Prior,
- Gemma M. Locke,
- Alina Meindl,
- Aoife A. Ryan and
- Mathias O. Senge
Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88
- induced distortion of the macrocyclic core. Due to their relatively large size and high electronegativity, halogens induce a conformational distortion of the porphyrin core that is significant compared to those induced by other substitution groups. As recently illustrated in a review by Kielmann and Senge
Graphical Abstract
Figure 1: 5-Halo-substituted porphyrins.
Figure 2: Expanded view (thermal ellipsoid) of compound 1 in the crystal showing (A) stacking, (B) tilted edg...
Figure 3: Expanded view (ball and stick) of compound 2 in the crystal showing (A) stacking, (B) bromine atoms...
Figure 4: Expanded view (ball and stick) of compound 3 in the crystal showing (A) stacking and (B) edge-on in...
Figure 5: Hirshfeld surfaces of compounds 1–3.
Figure 6: Contact percentages of compounds 1–3.
Figure 7: NSD charts for compounds 1–3.
Figure 8: Expanded view (thermal ellipsoid plot) of compound 2A showing (A) the edge-on and stacking interact...
Figure 9: 5-Halo-15-phenyl-substituted porphyrins.
Figure 10: Expanded view (thermal ellipsoid plot) of compound 4 showing (A) tilted alignment of porphyrin ring...
Figure 11: Expanded view (thermal ellipsoid plot) of compound 5 showing (A) porphyrin stacking and (B) Br···H ...
Figure 12: Expanded view (thermal ellipsoid plot) of compounds 6 (A and C) and 7 (B and D) showing (A) Br···H ...
Figure 13: 5,15-Di-halo-substituted porphyrins.
Figure 14: Expanded view (thermal ellipsoid plot) of compound 9 showing the Br···H interactions with (A) pyrro...
Figure 15: Expanded view (thermal ellipsoid plot) of compound 10 showing the (A) Br···H interactions with toly...
Figure 16: Expanded view (thermal ellipsoid plot) of compound 11 showing the (A) edge-on interactions, (B) edg...
Figure 17: Expanded view (thermal ellipsoid plot) of compound 13 showing (A) Br···H interactions with pyrrole ...
Figure 18: Expanded view (ball and stick) of compound 13A showing (A) Br···H interactions with pyrrole units a...
Figure 19: 5,10-Di-halo-substituted porphyrins.
Figure 20: Expanded view (ball and stick) of compound 16 showing (A) stacking, (B) head-to-tail alignment, (C)...
Figure 21: Honorable mentions of halogen-substituted porphyrins taken from the CSD database.
Figure 22: Series 1 – 5,15-di-halo-substituted porphyrins.
Figure 23: Series 2 – increasing number of halogen substituents.
Figure 24: Series 3 – 5,10-di-halo-substituted porphyrins.
Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones
- Jan Bartáček,
- Jan Svoboda,
- Martin Kocúrik,
- Jaroslav Pochobradský,
- Alexander Čegan,
- Miloš Sedlák and
- Jiří Váňa
Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84
- %; 85% ee), but the reaction times were very short (Scheme 7) [41]. In 2011, the groups of Hayashi and Chujo studied Pd complexes of diphosphacrown ethers [42]. The macrocyclic Pd complex PdL5 in combination with AgSbF6 or AgOTf was tested for the addition reaction of various arylboronic acids to 2
Graphical Abstract
Scheme 1: Synthesis of optically pure 4-phenylchroman-2-one [34].
Scheme 2: Synthesis of (R)-tolterodine [3].
Scheme 3: Catalytic cycle of the Pd(II)-catalysed 1,4-addition of organoboron reagents to enones [3,26,35].
Scheme 4: Enantioselective β-arylation of cyclohexanone [38].
Scheme 5: Application of L2/Pd(OAc)2 in the total synthesis of terpenes [8].
Scheme 6: Plausible catalytic cycle for the addition of phenylboronic acid to 2-cyclohexenone catalysed by L3...
Scheme 7: Microwave-assisted addition of phenylboronic acid to 2-cyclohexenone catalysed by L4/Pd2(dba)3·CHCl3...
Scheme 8: Plausible catalytic cycle of the addition of phenylboronic acid to 2-cyclohexenone catalysed by pal...
Scheme 9: Proposed catalytic cycle for the addition of phenylboronic acids to 2-cyclohexenone catalysed by Pd...
Scheme 10: Usage of addition reactions of boronic acids to various chromones in the syntheses of potentially a...
Scheme 11: Multigram-scale synthesis of ABBV-2222 [6].
Scheme 12: Application of the asymmetric addition of phenylboronic acid to a chromone derivative for the total...
Scheme 13: Plausible catalytic cycle for the addition of phenylboronic acid to 3-methyl-2-cyclohexenone cataly...
Scheme 14: Total syntheses of naturally occurring terpenoids [10,11].
Scheme 15: Use of the L9/Pd(TFA)2 catalytic system for the synthesis of intermediates of biologically active c...
Scheme 16: Usage of a Michael addition catalysed by L9/Pd(TFA)2 in the total synthesis of (–)-ar-tenuifolene [12].
Scheme 17: Synthesis of terpenoids by Michael addition to 3-methyl-2-cyclopentenone [13].
Scheme 18: Rh-catalysed isomerisation of 3-alkyl-3-arylcyclopentanones to 1-tetralones [53].
Scheme 19: Addition reaction of phenylboronic acid to 3-methyl-2-cyclohexenone catalysed by L9/Pd(TFA)2 in wat...
Scheme 20: Micellar nanoreactor PdL10c for the synthesis of flavanones [58].
Scheme 21: Plausible catalytic cycle for the desymmetrisation of polycyclic cyclohexenediones by the addition ...
Scheme 22: Attempt to use the catalytic system L2/Pd(TFA)2 for the addition of phenylboronic acid to 3-methyl-...
Scheme 23: Ring opening of an enantioenriched tetrahydropyran-2-one derivative as alternative strategy to line...
Scheme 24: Synthesis of biologically active compounds from addition products [14-16].
Scheme 25: Chiral 1,10-phenantroline derivative L15 as ligand for the Pd-catalysed addition reactions of pheny...
Scheme 26: The Rh-catalysed addition reaction of phenylboronic acid to a 3-substituted enone [20].
Scheme 27: Underdeveloped methodologies [14,15,65-67].
Scheme 28: Flowchart for the selection of the proper catalytic system.
Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects
- Shivani Gulati,
- Stephy Elza John and
- Nagula Shankaraiah
Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71
- electron-rich pyrazolylamine led to the formation of intermediate A. Simultaneously, intermediate B (condensation of arylgyoxal and primary amine 32b undergoes C=N addition with intermediate A. Intramolecular cyclization of C yields a macrocyclic intermediate D which is followed by p-TsOH-promoted ring
Graphical Abstract
Figure 1: Marketed drugs with acridine moiety.
Scheme 1: Synthesis of 4-arylacridinediones.
Scheme 2: Proposed mechanism for acridinedione synthesis.
Scheme 3: Synthesis of tetrahydrodibenzoacridinones.
Scheme 4: Synthesis of naphthoacridines.
Scheme 5: Plausible mechanism for naphthoacridines.
Figure 2: Benzoazepines based potent molecules.
Scheme 6: Synthesis of azepinone.
Scheme 7: Proposed mechanism for azepinone formation.
Scheme 8: Synthesis of benzoazulenen-1-one derivatives.
Scheme 9: Proposed mechanism for benzoazulene-1-one synthesis.
Figure 3: Indole-containing pharmacologically active molecules.
Scheme 10: Synthesis of functionalized indoles.
Scheme 11: Plausible mechanism for the synthesis of functionalized indoles.
Scheme 12: Synthesis of spirooxindoles.
Scheme 13: Synthesis of substituted spirooxindoles.
Scheme 14: Plausible mechanism for the synthesis of substituted spirooxindoles.
Scheme 15: Synthesis of pyrrolidinyl spirooxindoles.
Scheme 16: Proposed mechanism for pyrrolidinyl spirooxindoles.
Figure 4: Pyran-containing biologically active molecules.
Scheme 17: Synthesis of functionalized benzopyrans.
Scheme 18: Plausible mechanism for synthesis of benzopyran.
Scheme 19: Synthesis of indoline-spiro-fused pyran derivatives.
Scheme 20: Proposed mechanism for indoline-spiro-fused pyran.
Scheme 21: Synthesis of substituted naphthopyrans.
Figure 5: Marketed drugs with pyrrole ring.
Scheme 22: Synthesis of tetra-substituted pyrroles.
Scheme 23: Mechanism for silica-supported PPA-SiO2-catalyzed pyrrole synthesis.
Scheme 24: Synthesis of pyrrolo[1,10]-phenanthrolines.
Scheme 25: Proposed mechanism for pyrrolo[1,10]-phenanthrolines.
Figure 6: Marketed drugs and molecules containing pyrimidine and pyrimidinones skeletons.
Scheme 26: MWA-MCR pyrimidinone synthesis.
Scheme 27: Two proposed mechanisms for pyrimidinone synthesis.
Scheme 28: MWA multicomponent synthesis of dihydropyrimidinones.
Scheme 29: Proposed mechanism for dihydropyrimidinones.
Figure 7: Biologically active fused pyrimidines.
Scheme 30: MWA- MCR for the synthesis of pyrrolo[2,3-d]pyrimidines.
Scheme 31: Proposed mechanism for pyrrolo[2,3-d]pyrimidines.
Scheme 32: Synthesis of substituted pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 33: Probable pathway for pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 34: Synthesis of pyridopyrimidines.
Scheme 35: Plausible mechanism for the synthesis of pyridopyrimidines.
Scheme 36: Synthesis of dihydropyridopyrimidine and dihydropyrazolopyridine.
Scheme 37: Proposed mechanism for the formation of dihydropyridopyrimidine.
Scheme 38: Synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 39: Plausible mechanism for the synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 40: Synthesis of decorated imidazopyrimidines.
Scheme 41: Proposed mechanism for imidazopyrimidine synthesis.
Figure 8: Pharmacologically active molecules containing purine bases.
Scheme 42: Synthesis of aza-adenines.
Scheme 43: Synthesis of 5-aza-7-deazapurines.
Scheme 44: Proposed mechanism for deazapurines synthesis.
Figure 9: Biologically active molecules containing pyridine moiety.
Scheme 45: Synthesis of steroidal pyridines.
Scheme 46: Proposed mechanism for steroidal pyridine.
Scheme 47: Synthesis of N-alkylated 2-pyridones.
Scheme 48: Two possible mechanisms for pyridone synthesis.
Scheme 49: Synthesis of pyridone derivatives.
Scheme 50: Postulated mechanism for synthesis of pyridone.
Figure 10: Biologically active fused pyridines.
Scheme 51: Benzimidazole-imidazo[1,2-a]pyridines synthesis.
Scheme 52: Mechanism for the synthesis of benzimidazole-imidazo[1,2-a]pyridines.
Scheme 53: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives.
Scheme 54: Proposed mechanism for spiro-pyridines.
Scheme 55: Functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 56: Mechanism postulated for macrocyclane-fused pyrazolo[3,4-b]pyridine.
Scheme 57: Generation of pyrazolo[3,4-b]pyridines.
Scheme 58: Proposed mechanism for the synthesis of pyrazolo[3,4-b]pyridines.
Scheme 59: Proposed mechanism for the synthesis of azepinoindole.
Figure 11: Pharmaceutically important molecules with quinoline moiety.
Scheme 60: Povarov-mediated quinoline synthesis.
Scheme 61: Proposed mechanism for Povarov reaction.
Scheme 62: Synthesis of pyrazoloquinoline.
Scheme 63: Plausible mechanism for pyrazoloquinoline synthesis.
Figure 12: Quinazolinones as pharmacologically significant scaffolds.
Scheme 64: Four-component reaction for dihydroquinazolinone.
Scheme 65: Proposed mechanism for dihydroquinazolinones.
Scheme 66: Synthesis purine quinazolinone and PI3K-δ inhibitor.
Scheme 67: Synthesis of fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 68: Proposed mechanism for fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 69: On-water reaction for synthesis of thiazoloquinazolinone.
Scheme 70: Proposed mechanism for the thiazoloquinazolinone synthesis.
Scheme 71: β-Cyclodextrin-mediated synthesis of indoloquinazolinediones.
Scheme 72: Proposed mechanism for synthesis of indoloquinazolinediones.
Figure 13: Triazoles-containing marketted drugs and pharmacologically active molecules.
Scheme 73: Cu(I) DAPTA-catalyzed 1,2,3-triazole formation.
Scheme 74: Mechanism for Cu(I) DAPTA-catalyzed triazole formation.
Scheme 75: Synthesis of β-hydroxy-1,2,3-triazole.
Scheme 76: Proposed mechanism for synthesis of β-hydroxy-1,2,3-triazoles.
Scheme 77: Synthesis of bis-1,2,4-triazoles.
Scheme 78: Proposed mechanism for bis-1,2,4-triazoles synthesis.
Figure 14: Thiazole containing drugs.
Scheme 79: Synthesis of a substituted thiazole ring.
Scheme 80: Synthesis of pyrazolothiazoles.
Figure 15: Chromene containing drugs.
Scheme 81: Magnetic nanocatalyst-mediated aminochromene synthesis.
Scheme 82: Proposed mechanism for the synthesis of chromenes.
Valorisation of plastic waste via metal-catalysed depolymerisation
- Francesca Liguori,
- Carmen Moreno-Marrodán and
- Pierluigi Barbaro
Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53
- mediated by commercially available Ru homogeneous catalysts [148]. The process afforded C16 to C44 mixtures of macrocyclic oligobutadienes with up to 98% selectivity at moderate conversions (59–88%) using first-generation Ru complexes bearing a tricyclohexylphosphine (PCy3) ligand, mild reaction
Graphical Abstract
Figure 1: Potential classification of plastic recycling processes. The area covered by the present review is ...
Figure 2: EG produced during glycolytic depolymerisation of PET using DEG + DPG as solvent and titanium(IV) n...
Scheme 1: Simplified representation of the conversion of 1,4-PBD to C16–C44 macrocycles using Ru metathesis c...
Figure 3: Main added-value monomers obtainable by catalytic depolymerisation of PET via chemolytic methods.
Scheme 2: Hydrogenolytic depolymerisation of PET by ruthenium complexes.
Scheme 3: Depolymerisation of PET via catalytic hydrosilylation by Ir(III) pincer complex.
Scheme 4: Catalytic hydrolysis (top) and methanolysis (bottom) reactions of PET.
Scheme 5: Depolymerisation of PET by glycolysis with ethylene glycol.
Figure 4: Glycolysis of PET: evolution of BHET yield over time, with and without zinc acetate catalyst (196 °...
Scheme 6: Potential activated complex for the glycolysis reaction of PET catalysed by metallated ILs and evol...
Scheme 7: One-pot, two-step process for PET repurposing via chemical recycling.
Scheme 8: Synthetic routes to PLA.
Scheme 9: Structures of the zinc molecular catalysts used for PLA-methanolysis in various works. a) See [265], b) ...
Scheme 10: Depolymerisation of PLLA by Zn–N-heterocyclic carbene complex.
Scheme 11: Salalen ligands.
Scheme 12: Catalytic hydrogenolysis of PLA.
Scheme 13: Catalytic hydrosilylation of PLA.
Scheme 14: Hydrogenative depolymerisation of PBT and PCL by molecular Ru catalysts.
Scheme 15: Glycolysis reaction of PCT by diethylene glycol.
Scheme 16: Polymerisation–depolymerisation cycle of 3,4-T6GBL.
Scheme 17: Polymerisation–depolymerisation cycle of 2,3-HDB.
Scheme 18: Hydrogenative depolymerisation of PBPAC by molecular Ru catalysts.
Scheme 19: Catalytic hydrolysis (top), alcoholysis (middle) and aminolysis (bottom) reactions of PBPAC.
Scheme 20: Hydrogenative depolymerisation of PPC (top) and PEC (bottom) by molecular Ru catalysts.
Scheme 21: Polymerisation-depolymerisation cycle of BEP.
Scheme 22: Hydrogenolysis of polyamides using soluble Ru catalysts.
Scheme 23: Catalytic depolymerisation of epoxy resin/carbon fibres composite.
Scheme 24: Depolymerisation of polyethers with metal salt catalysts and acyl chlorides.
Scheme 25: Proposed mechanism for the iron-catalysed depolymerisation reaction of polyethers. Adapted with per...
Synthetic strategies of phosphonodepsipeptides
- Jiaxi Xu
Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41
- nucleophilic esterification of potassium 1-(N-benzyloxycarbonylamino)alkylphosphonates 172 with alkyl halides in the presence of 18-crown-6. They also prepared a phosphonodepsidipeptide 174 with ethyl chloroacetate (173) as an electrophile (Scheme 33) [53]. The macrocyclic peptidyl phosphonodepsipeptide 180
- was designed on the basis of the acyclic conformational analog bound to the aspartic protease penicillopepsin. Dimethyl N-Cbz-1-amino-2-(naphthalen-2-yl)ethylphosphonate 176 was first prepared from 7-bromo-3,4-dihydronaphthalen-1(2H)-one (175) and further transformed to the macrocyclic peptidyl
- phosphonic monomethyl ester 177. The latter compound was alkylated with methyl 3-phenyl-2-trifluoromethanesulfonyloxypropanoate (178) to produce the macrocyclic peptidyl phosphonodepsipeptide 179, which was selectively hydrolyzed with TMSBr and treated with Dowex-Na+ to afford the macrocyclic peptidyl
Graphical Abstract
Figure 1: Phosphonopeptides, phosphonodepsipeptides, peptides, and depsipeptides.
Figure 2: The diverse strategies for phosphonodepsipeptide synthesis.
Scheme 1: Synthesis of α-phosphonodepsidipeptides as inhibitors of leucine aminopeptidase.
Figure 3: Structure of 2-hydroxy-2-oxo-3-[(phenoxyacetyl)amino]-1,2-oxaphosphorinane-6-carboxylic acid (16).
Scheme 2: Synthesis of α-phosphonodepsidipeptide 17 as coupling partner for cyclen-containing phosphonodepsip...
Scheme 3: Synthesis of α-phosphonodepsidipeptides containing enantiopure hydroxy ester as VanX inhibitors.
Scheme 4: Synthesis of α-phosphonodepsidipeptides as VanX inhibitors.
Scheme 5: Synthesis of optically active α-phosphonodepsidipeptides as VanX inhibitors.
Scheme 6: The synthesis of phosphonodepsipeptides through a thionyl chloride-catalyzed esterification of N-Cb...
Scheme 7: Synthesis of α-phosphinodipeptidamide as a hapten.
Scheme 8: Synthesis of α-phosphonodepsioctapeptide 41.
Scheme 9: Synthesis of phosphonodepsipeptides via an in situ-generated phosphonochloridate.
Scheme 10: Synthesis of α-phosphonodepsitetrapeptides 58 as inhibitors of the aspartic peptidase pepsin.
Scheme 11: Synthesis of a β-phosphonodepsidipeptide library 64.
Scheme 12: Synthesis of another β-phosphonodepsidipeptide library.
Scheme 13: Synthesis of γ-phosphonodepsidipeptides.
Scheme 14: Synthesis of phosphonodepsipeptides 85 as folylpolyglutamate synthetase inhibitors.
Scheme 15: Synthesis of the γ-phosphonodepsitripeptide 95 as an inhibitor of γ-gutamyl transpeptidase.
Scheme 16: Synthesis of phosphonodepsipeptides as inhibitors and probes of γ-glutamyl transpeptidase.
Scheme 17: Synthesis of phosphonyl depsipeptides 108 via DCC-mediated condensation and oxidation.
Scheme 18: Synthesis of phosphonodepsipeptides 111 with BOP and PyBOP as coupling reagents.
Scheme 19: Synthesis of optically active phosphonodepsipeptides with BOP and PyBOP as coupling reagents.
Scheme 20: Synthesis of phosphonodepsipeptides with BroP and TPyCIU as coupling reagents.
Scheme 21: Synthesis of a phosphonodepsipeptide hapten with BOP as coupling reagent.
Scheme 22: Synthesis of phosphonodepsitripeptide with BOP as coupling reagent.
Scheme 23: Synthesis of norleucine-derived phosphonodepsipeptides 135 and 138.
Scheme 24: Synthesis of norleucine-derived phosphonodepsipeptides 141 and 144.
Scheme 25: Solid-phase synthesis of phosphonodepsipeptides.
Scheme 26: Synthesis of phosphonodepsidipeptides via the Mitsunobu reaction.
Scheme 27: Synthesis of γ-phosphonodepsipeptide via the Mitsunobu reaction.
Scheme 28: Synthesis of phosphonodepsipeptides via a multicomponent condensation reaction.
Scheme 29: Synthesis of phosphonodepsipeptides with a functionalized side-chain via a multicomponent condensat...
Scheme 30: High yielding synthesis of phosphonodepsipeptides via a multicomponent condensation.
Scheme 31: Synthesis of optically active phosphonodepsipeptides via a multicomponent condensation reaction.
Scheme 32: Synthesis of N-phosphoryl phosphonodepsipeptides.
Scheme 33: Synthesis of phosphonodepsipeptides via the alkylation of phosphonic monoesters.
Scheme 34: Synthesis of phosphonodepsipeptides as inhibitors of aspartic protease penicillopepsin.
Scheme 35: Synthesis of phosphonodepsipeptides as prodrugs.
Scheme 36: Synthesis of phosphonodepsithioxopeptides 198.
Scheme 37: Synthesis of phosphonodepsipeptides.
Scheme 38: Synthesis of phosphonodepsipeptides with C-1-hydroxyalkylphosphonic acid.
Scheme 39: Synthesis of phosphonodepsipeptides with C-1-hydroxyalkylphosphonate via the rhodium-catalyzed carb...
Scheme 40: Synthesis of phosphonodepsipeptides with a C-1-hydroxyalkylphosphonate motif via a copper-catalyzed...
Au(III) complexes with tetradentate-cyclam-based ligands
- Ann Christin Reiersølmoen,
- Thomas N. Solvi and
- Anne Fiksdahl
Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18
- binding properties [25] and reactions with bovine serum albumin [27]. Cyclam is known as a tetraamino-macrocyclic ligand, which binds strongly to give complexes with many transition metal cations. While catalytic applications of square planar cyclam complexes are reported for metals, such as Ni [30][31
- macrocyclic byproduct (14%) was formed by condensation of three units of diamine A and malonyl dichloride. To inhibit the formation of the trimer, we decided to prepare the cyclams in an indirect way. In fact, increased yields of cyclam derivative 2a (68% yield over three steps) were obtained by malonyl
Graphical Abstract
Scheme 1: Synthetic protocols for the preparation of potential ligands 1–4.
Scheme 2: Reduction of diamides 1a,b and tetraamides 2a,b.
Scheme 3: Au(III) coordination conditions for ligands 5a,b and 6a,b. Coordination of 5b was unsuccessful.
Figure 1: 1H NMR study of the formation of complex 6a-Au(III) by AuCl3 coordination to ligand 6a.
Insight into functionalized-macrocycles-guided supramolecular photocatalysis
- Minzan Zuo,
- Krishnasamy Velmurugan,
- Kaiya Wang,
- Xueqi Tian and
- Xiao-Yu Hu
Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15
- with various macrocyclic hosts as well as on the role of macrocyclic-hosts-assisted hybrid materials in energy transfer. To keep the clarity of this review, the macrocycles are categorized into the most commonly used supramolecular hosts, including crown ethers, cyclodextrins, cucurbiturils
- advantages of the macrocycles in photocatalysis including: i) substrate selectivity, ii) controllability of the rate of photochemical reactions, iii) the close proximity to substrates in a confined space, iv) the generation of a stabilized high-energy transition state, and v) macrocyclic-cavity-size
- via photophysical analyses is relatively important. Hence, this review aims to summarize the photochemical transformation and catalytic reactivity of different guests within the various macrocyclic hosts of various sizes and shapes based on molecular recognition as well as the role of macrocyclic-host
Graphical Abstract
Figure 1: Chemical structures of representative macrocycles.
Figure 2: Ba2+-induced intermolecular [2 + 2]-photocycloaddition of crown ether-functionalized substrates 1 a...
Figure 3: Energy transfer system constructed of a BODIPY–zinc porphyrin–crown ether triad assembly bound to a...
Figure 4: The sensitizer 5 was prepared by a flavin–zinc(II)–cyclen complex for the photooxidation of benzyl ...
Figure 5: Enantiodifferentiating Z–E photoisomerization of cyclooctene sensitized by a chiral sensitizer as t...
Figure 6: Structures of the modified CDs as chiral sensitizing hosts. Adapted with permission from [24], Copyrigh...
Figure 7: Supramolecular 1:1 and 2:2 complexations of AC with the cationic β-CD derivatives 16–21 and subsequ...
Figure 8: Construction of the TiO2–AuNCs@β-CD photocatalyst. Republished with permission of The Royal Society...
Figure 9: Visible-light-driven conversion of benzyl alcohol to H2 and a vicinal diol or to H2 and benzaldehyd...
Figure 10: (a) Structures of CDs, (b) CoPyS, and (c) EY. Republished with permission of The Royal Society of C...
Figure 11: Conversion of CO2 to CO by ReP/HO-TPA–TiO2. Republished with permission of The Royal Society of Che...
Figure 12: Thiacalix[4]arene-protected TiO2 clusters for H2 evolution. Reprinted with permission from [37], Copyri...
Figure 13: 4-Methoxycalix[7]arene film-based TiO2 photocatalytic system. Reprinted from [38], Materials Today Chem...
Figure 14: (a) Photodimerization of 6-methylcoumarin (22). (b) Catalytic cycle for the photodimerization of 22...
Figure 15: Formation of a supramolecular PDI–CB[7] complex and structures of monomers and the chain transfer a...
Figure 16: Ternary self-assembled system for photocatalytic H2 evolution (a) and structure of 27 (b). Figure 16 reprodu...
Figure 17: Structures of COP-1, CMP-1, and their substrate S-1 and S-2.
Figure 18: Supramolecular self-assembly of the light-harvesting system formed by WP5, β-CAR, and Chl-b. Reprod...
Figure 19: Photocyclodimerization of AC based on WP5 and WP6.
The fluorescence of a mercury probe based on osthol
- Guangyan Luo,
- Zhishu Zeng,
- Lin Zhang,
- Zhu Tao and
- Qianjun Zhang
Beilstein J. Org. Chem. 2021, 17, 22–27, doi:10.3762/bjoc.17.3
- Guangyan Luo Zhishu Zeng Lin Zhang Zhu Tao Qianjun Zhang Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China 10.3762/bjoc.17.3 Abstract The ability of osthol (OST) to recognize mercury ions in aqueous solution was studied using
Graphical Abstract
Figure 1: (A) Fluorescence spectra of OST (c = 3.0 × 10−5 mol∙L−1) upon the addition of various metal ions. (...
Figure 2: Metal ion selectivity of OST–Hg2+ (c = 3.0 × 10−5 mol∙L−1) in the presence of 1.2 × 10−4 mol∙L−1 of...
Figure 3: Fluorescence spectra of OST (c = 3 × 10−5 mol∙L−1) in H2O/CH3OH 97:3, v/v in the presence of an inc...
Figure 4: The standard Job curve of mercury ions to OST (c = 3.0 × 10−5 mol∙L−1) at 406 nm (pH 7.0, H2O/CH3OH...
Figure 5: Mass spectrum of the probe with Hg2+.
Figure 6: 1H NMR titration spectra recorded for OST (c = 5 × 10−4 mol∙L−1) during the addition of different m...
Figure 7: The binding mode of OST and Hg2+.
Selected peptide-based fluorescent probes for biological applications
- Debabrata Maity
Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247
- insulin Schmuck and co-workers reported a supramolecular ensemble in combination of a pyrene-tagged amphiphilic peptide beacon (6) and a macrocyclic host (cucurbit[8]uril, CB[8]) for ratiometric fluorescent detection of amino acid derivatives, specific peptides, and proteins in aqueous media (Figure 6
Graphical Abstract
Figure 1: Three different type of peptide-based fluorescent probes and their interaction with nucleic acids a...
Figure 2: A) Molecular structure of peptidic probe 1, Inset: HeLa cells incubated with peptide 1 (50 μM), sho...
Figure 3: A) Molecular structure of probe 2; B) fluorescence emission spectra for the titration of a 10 μM so...
Figure 4: A) Molecular structure of 3; B) fluorescence emission spectra for the titration of a 10 μM solution...
Figure 5: A) Molecular structure of 4 and 5; B) fluorescence spectra for the titration of a 0.5 μM solution o...
Figure 6: A) Molecular structure of 6; B) possible binding mode of pyrene termini of 6 to CB[8] according to ...
Figure 7: A) Molecular structure of peptidic probes 7 and 8; B) fluorescence emission spectra of probe 7 (5.0...
Figure 8: Top: Molecular structure of 9; bottom: A) fluorescence response of 9 (500 nM) upon addition of β-tr...
Figure 9: Top: Molecular structures of 10 and 11; bottom: A) fluorescence emission spectra of 10 (1.0 µM, λex...
Figure 10: A) Structure of two peptide amphiphiles 12 and 13; B) fluorescent spectra (λex = 400 nm) from a tit...
Figure 11: a) Molecular structure of peptide 14; b) the coordinate represents the states of sensor at differen...
