Search results
Search for "structural modification" in Full Text gives 44 result(s) in Beilstein Journal of Organic Chemistry.
Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds
- Natalya Akhmetdinova,
- Ilgiz Biktagirov and
- Liliya Kh. Faizullina
Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185
- multiple stereocenters, including contiguous quaternary carbons. As a result, the carboborative ring contraction reaction is conveniently used for structural modification of natural products containing a cyclohexene ring and in the synthesis of new compounds to increase their activity, metabolic stability
Graphical Abstract
Scheme 1: Ozonolysis–cyclization sequence in the synthesis of echinopine A (3).
Scheme 2: Ozonolysis–cyclization sequence in the synthesis of taiwaniaquinoids 7–12.
Figure 1: Iridoid skeleton.
Scheme 3: Ozonolysis–cyclization sequence in the synthesis of compounds 17a,b, 18 and 19 with iridoid topolog...
Scheme 4: Oxidation–aldol condensation sequence in the synthesis of compounds 21 and 23 with iridoid topology....
Scheme 5: Oxidation–aldol condensation sequence in the synthesis of compounds 29 and 30 with iridoid topology....
Scheme 6: Method for ring contraction in the absence of a double bond in a six-membered ring of triterpenoids....
Scheme 7: Oxidation–Dieckmann cyclization sequence in the synthesis of a new nortriterpenoid 39.
Scheme 8: Oxidation–Dieckmann cyclization sequence in the synthesis of 18,19-di-nor-cholesterol (40).
Scheme 9: Oxidation–cyclization sequence in the synthesis of 3-ethyl-substituted betulinic acid derivatives 49...
Scheme 10: Benzilic acid-type rearrangement in the synthesis of 4β-acetoxyprobotryane-9β,15α-diol (52).
Scheme 11: Benzilic acid-type rearrangement in the synthesis of (−)-taiwaniaquinone H (11).
Scheme 12: Benzilic acid-type rearrangement in the synthesis of dactylicapnosines A (63) and B (64).
Scheme 13: Aza-benzilic acid-type rearrangement in the synthesis of (+)-stephadiamine (71).
Scheme 14: α-Ketol rearrangement in the synthesis of saffloneoside (73).
Scheme 15: Conversion of (−)-preaustinoid A (80) to (−)-preaustinoid B (81) via α-ketol rearrangement.
Scheme 16: α-Ketol rearrangement in the synthesis of 2,8-oxymethano-bridged diquinane 90.
Scheme 17: Oxidative ring contraction during the synthesis of (+)-cuparene (91) and (+)-tochuinylacetate (92).
Scheme 18: Semipinacol rearrangement in the synthesis of diterpenoids 97–100.
Scheme 19: Co-catalyzed homoallyl-type rearrangement in the syntheses of meroterpenes 106–109.
Scheme 20: Ring contraction reaction promoted by TTN·3H2O and HTIB in the synthesis of indanes.
Scheme 21: Rearrangement involving a hypervalent iodine compound in the synthesis of derivative 120.
Scheme 22: Wolff rearrangement in the synthesis of taiwaniaquinones A (7), F (8), taiwaniaquinols B (10), D (1...
Scheme 23: Wolff rearrangement in the synthesis of cheloviolene C (128), seconorrisolide B (129), and seconorr...
Scheme 24: Wolff rearrangement in the synthesis of (−)-pavidolide B (134).
Scheme 25: Wolff rearrangement in the synthesis of presilphiperfolan-8-ol (141).
Scheme 26: Photochemical rearrangement in the synthesis of cyclopentane derivatives 147a,b.
Scheme 27: Synthesis of cyclopentane derivatives 147a and 151.
Scheme 28: Photochemical rearrangement in the synthesis of cyclopentane derivative 153.
Scheme 29: Photochemical rearrangement in the synthesis of tricyclic ketones 155, 156.
Scheme 30: Photochemical rearrangement in the synthesis of cis/trans salts 160.
Figure 2: Scope of the photoinduced carboborative ring contraction of steroids. Reaction conditions: steroid ...
Scheme 31: Photoinduced carboborative ring contraction in the synthesis of artalbic acid (180).
Scheme 32: Synthetic versatility of the photoinduced carboborative ring contraction.
Scheme 33: Methods of disclosure of epoxide 189.
Scheme 34: Methods of disclosure of epoxide 190.
Scheme 35: Rearrangement of α,β-epoxy ketone 197.
Scheme 36: Acid-induced rearrangement in the synthesis of perhydrindane ketones 202 and 205.
Scheme 37: Rearrangement of epoxyketone 208 in the synthesis of huperzine Q (206).
Scheme 38: Rearrangement of epoxide 212 under the action of Grignard reagent.
Scheme 39: Semipinacol rearrangement of epoxide 220 in the synthesis of (−)-citrinadin A (217) and (+)-citrina...
Scheme 40: Semipinacol rearrangement of epoxide 225 in the synthesis of hamigeran G (223).
Scheme 41: Semipinacol rearrangement of epoxide 231 in the synthesis of (−)-spirochensilide A (228).
Scheme 42: Wagner–Meerwein rearrangement in the synthesis of compound 234 with iridoid topology.
Scheme 43: Wagner–Meerwein rearrangement in the synthesis of compound 238 with iridoid topology.
Scheme 44: Wagner–Meerwein rearrangement in the synthesis of compound 241 with iridoid topology.
Scheme 45: Wagner–Meerwein rearrangement in the synthesis of lupane derivatives 245, 246, 248, and 249.
Scheme 46: Wagner–Meerwein rearrangement in the synthesis of weisaconitine D (252) and cardiopetaline (255).
Scheme 47: Wagner–Meerwein rearrangement in the synthesis of cardiopetaline (255).
Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications
- Meng Qiu,
- Jing Du,
- Nai-Te Yao,
- Xin-Yue Wang and
- Han-Yuan Gong
Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106
- – particularly those incorporating additional heteroatoms within the helical π-conjugated framework – remains lacking. This review addresses this gap by systematically summarizing recent advances (from the past five years) in the synthesis, structural modification, and chiroptical properties of nitrogen-doped
Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts
- Mandeep K. Chahal
Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257
- batteries, due to the ease of their structural modification, rich redox chemistry, and robust coordination M–N4 environment [100][101][102][103][104][105]. The key processes employed in energy transfer and storage are the oxygen reduction reaction (ORR), hydrogen evolution reaction (HER), and oxygen
Graphical Abstract
Figure 1: Chemical structures of the main tetrapyrrolic macrocycles studied in this review for their role as ...
Figure 2: Calix[4]pyrroles 3 and 4 and an their acyclic analogue 5 used for the transformation of Danishefsky...
Figure 3: Calixpyrrole-based organocatalysts 11 and 12 for the diastereoselective addition reaction of TMSOF ...
Figure 4: (a) Chemical structures of macrocyclic organocatalysts used for the synthesis of cyclic carbonates ...
Figure 5: Cuprous chloride-catalyzed aziridination of styrene (22) by chloramine-T (23) providing 1-tosyl-2-p...
Figure 6: Chemical structures of the various porphyrin macrocycles (18, 25–41) screened as potential catalyst...
Figure 7: Organocatalytic activity of distorted porphyrins explored by Senge and co-workers. Planar macrocycl...
Figure 8: Chemical structures of H2EtxTPP (x = 0, 2, 4, 6, 8) compounds with incrementally increasing nonplan...
Figure 9: Chemical structures of OxP macrocycles tested as potential organocatalysts for the conjugate additi...
Figure 10: a) Fundamental structure of the J-aggregates of diprotonated TPPS3 53 and b) its use as a catalyst ...
Figure 11: Chemical structures of amphiphilic porphyrin macrocycles used as pH-switchable catalysts based on i...
Figure 12: a) Chemical structures of porphyrin macrocycles for the cycloaddition of CO2 to N-alkyl/arylaziridi...
Figure 13: Electron and energy-transfer processes typical for excited porphyrin molecules (Por = porphyrin mac...
Figure 14: Proposed mechanism for the light-induced α-alkylation of aldehydes with EDA in the presence of H2TP...
Figure 15: a) Chemical structures of porphyrins screened as photoredox catalysts, b) model reaction of furan (...
Figure 16: Porphyrin macrocycles H2TPP (18) and PPIX 78 as photoreductants for the red light-induced C–H aryla...
Figure 17: Porphyrin macrocycles H2TPP (18) and PPIX 78 as photoredox catalyst for (a) α-alkylation of an alde...
Figure 18: Corrole macrocycles 98–100 as photoredox catalysts for C–H arylation and borylation reactions. Adap...
Figure 19: Proposed catalytic cycle of electrocatalytic generation of H2 evolution using tetrapyrrolic macrocy...
Figure 20: a) Chemical structures of tetrapyrrolic macrocycles 109, 73, and 110 used for oxygen reductions in ...
Figure 21: a) Absorption spectra (left) of the air-saturated DCE solutions containing: 5 × 10−5 M H2TPP (black...
Figure 22: Chemical structures of N,N’-dimethylated saddle-distorted porphyrin isomers, syn-Me2P 111 and anti-...
Figure 23: Reaction mechanisms for the two-electron reduction of O2 by a) syn-Me2Iph 113 and b) anti-Me2Iph 114...
Figure 24: O2/H2O2 interconversion using methylated saddle-distorted porphyrin and isophlorin (reduced porphyr...
Figure 25: Chemical structures of distorted dodecaphenylporphyrin macrocycle 117 and its diprotonated form 118...
The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives
- Sondos A. J. Almahmoud,
- Joseph Cameron,
- Dylan Wilkinson,
- Michele Cariello,
- Claire Wilson,
- Alan A. Wiles,
- Peter J. Skabara and
- Graeme Cooke
Beilstein J. Org. Chem. 2024, 20, 2921–2930, doi:10.3762/bjoc.20.244
- properties. Due to the low solubility of violanthrone in the majority of organic solvents, special attention has been drawn to its dihydroxy derivative (Figure 1), which allows further modification to the materials via etherification or esterification [29][30]. There has been a report on the structural
- modification of dihydroxyviolanthrone where the effect of three alkoxy substituents on the 16,17-bis(2-ethylhexyloxy)anthra[9,1,2-cde]benzo[rst]pentaphene-5,10-dione, on aggregation and photovoltaic properties was studied [30]. It was found that derivatives with the shortest linear alkyl chain (n-hexyl
Graphical Abstract
Figure 1: Chemical structures of violanthrone and dihydroxyviolanthrone.
Figure 2: Chemical structures of 2b and 3b.
Scheme 1: Synthesis of compounds 2a–c and 3a–c.
Figure 3: Optimised ground state geometries of compounds 2 and 3 calculated using B3LYP/6-311G(d,p) in the ga...
Figure 4: Views of the crystal structure of 3b (left, shows displacement ellipsoids drawn at 50% probability ...
Figure 5: Absorption spectra of 3a–c measured in dichloromethane solution (1 × 10−5 M).
Figure 6: SWV (left) and CV (right) of compound 3a–c (in dichloromethane 1 × 10−3 M) (V vs Fc/Fc+).
Factors influencing the performance of organocatalysts immobilised on solid supports: A review
- Zsuzsanna Fehér,
- Dóra Richter,
- Gyula Dargó and
- József Kupai
Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183
- influence on the properties and thus performance of the resulting heterogeneous catalyst. However, immobilisation and structural modification introduce additional steps in the synthesis of the catalyst. Moreover, the catalytic activity and selectivity of immobilised catalysts are often lower than those of
Graphical Abstract
Scheme 1: Esterification of oleic acid (1) with propylsulfonic acid (Pr-SO3H)-functionalised mesoporous silic...
Scheme 2: Using confinement of organocatalytic units for improving the enantioselectivity of silica-supported...
Scheme 3: Michael addition catalysed by cinchona thiourea immobilised on magnetic nanoparticles (13).
Scheme 4: Michael addition catalysed by cinchona thiourea in the presence of magnetic nanoparticles.
Scheme 5: Benzoin condensation catalysed by N-benzylthiazolium salt attached to mesoporous material.
Scheme 6: Photoinduced RAFT polymerisation of n-butyl acrylate (19) catalysed by silica nanoparticle-supporte...
Scheme 7: Pressure and temperature dependence of the 1,4-addition of propanal to trans-β-nitrostyrene under c...
Scheme 8: α-Amination of ethyl 2-oxocyclopentanecarboxylate catalysed by PS-THU which could be recycled over ...
Scheme 9: Preparation of supported catalysts C29–C31 from cinchona squaramides 29–31 modified with a primary ...
Scheme 10: Application of PGMA-supported organocatalysts C29–C31 in the asymmetric Michael addition of pentane...
Scheme 11: Alcoholytic desymmetrisation of a cyclic anhydride 34 catalysed by polyamide-supported cinchona sul...
Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations
- Ryo Tanifuji and
- Hiroki Oguri
Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151
- pentacyclic scaffolds. The designed and chemically synthesized substrate analog 96 was tolerated by the key NRPS module SfmC despite the structural modification (Scheme 10A). In vitro enzymatic conversion of 96 with tyrosine derivative 86 [103] followed by the addition of KCN concisely furnished the
Graphical Abstract
Scheme 1: Targeted natural products and key enzymatic transformations in the chemo-enzymatic total syntheses ...
Scheme 2: Biosynthetic pathway to brassicicenes in Pseudocercospora fijiensis [14]. (A) Cyclization phase catalyz...
Scheme 3: Chemo-enzymatic total synthesis of cotylenol (1) and brassicicenes. (A) Chemical cyclization phase....
Scheme 4: (A) Biosynthetic pathway for trichodimerol (2) in Penicillium chrysogenum. (B) Chemo-enzymatic tota...
Scheme 5: (A) Proposed biosynthetic pathway for chalcomoracin (3) in Morus alba. (B) Outline of the biosynthe...
Scheme 6: (A) Chemo-enzymatically synthesized natural products by using the originally identified MaDA. (B) M...
Scheme 7: Proposed biosynthetic mechanism of tylactone (4) in Streptomyces fradiae.
Scheme 8: (A) Chemical synthesis and cascade enzymatic transformations of cyclization precursors. (B) Late-st...
Scheme 9: Proposed biosynthetic mechanism of saframycin A (5) in Streptomyces lavendulae.
Scheme 10: (A) Chemo-enzymatic total synthesis of saframycin A (5) and jorunnamycin A (103). (B) Chemo-enzymat...
N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction
- Grigory Kantin,
- Pavel Golubev,
- Alexander Sapegin,
- Alexander Bunev and
- Dmitry Dar’in
Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136
- circumstances, considerably impacting their pharmacological utility [19][20], Moreover, the conventional CRBN recruiters restrict structural modification options necessary to maintain satisfactory affinity for the E3-ligase [21][22][23][24]. These limitations underscore the relevance of expanding the chemical
Graphical Abstract
Figure 1: Glutarimide-based immunomodulatory drugs (IMiDs) and CRBN ligands.
Scheme 1: Main literature approaches towards α-hetaryl glutarimides 1 (routes A and B) and new “diazo” method...
Scheme 2: Preparation of diazo reagent 5.
Scheme 3: Scope of NH insertion reaction of N-Boc-α-diazo glutarimide and various N-heterocycles. aIsolated y...
Figure 2: Examples of α-carbonyl NH-heterocycles for which N–H insertion products could not be obtained.
Scheme 4: Examples of N-deprotection of α-modified glutarimides 1.
Scheme 5: Preparation of NH2-containing derivative 10 via reduction of 6n.
Quinoxaline derivatives as attractive electron-transporting materials
- Zeeshan Abid,
- Liaqat Ali,
- Sughra Gulzar,
- Faiza Wahad,
- Raja Shahid Ashraf and
- Christian B. Nielsen
Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124
- of structural modification, the introduction of various functional groups into Qx derivatives has allowed for the precise control of energy levels, bandgaps, and carrier transport properties. For instance, Sharma et al. fine-tuned the intermolecular charge transfer (ICT) transitions and emission
Graphical Abstract
Figure 1: Structures of some of the most versatile Qx scaffolds; dashed lines indicate the substitution sites...
Figure 2: Qx-derived polymer acceptors.
Figure 3: Qx-derived small molecule NFAs.
Figure 4: Qx-derived small molecule NFAs.
Figure 5: Dyes and sensitizers based on Qx auxiliary acceptors or bridging units.
Figure 6: Qx-derived n-type transistor materials.
Figure 7: Qx-derived ETM and TADF emitters.
Figure 8: Qx-derived chromophores.
Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials
- Jessica Villegas,
- Bryce C. Ball,
- Katelyn M. Shouse,
- Caleb W. VanArragon,
- Ashley N. Wasserman,
- Hannah E. Bhakta,
- Allen G. Oliver,
- Danielle A. Orozco-Nunnelly and
- Jeffrey M. Pruet
Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108
- structural modification, this was chosen as the path towards enhancing the activity of B1. As shown in Scheme 5, we reduced B1 to produce B14, which was then screened against our panel of microbial organisms (Table 2). We were very pleased with the results of B14, representing a near universal improvement
Graphical Abstract
Figure 1: Zones of inhibition for 1 mg of evaporated methanolic (MeOH) extracts from various parts of the A. ...
Scheme 1: General route to berberine variants, displaying the numbering system for the berberine ring.
Scheme 2: Synthesis of new berberine variants. Reductive amination to a secondary amine was followed by cycli...
Figure 2: X-ray crystal structures of the oxidation byproducts a) B4 (CCDC 2271457) and b) B6 (CCDC 2271458; ...
Scheme 3: Direct modification of the original berberine structure.
Scheme 4: Preparation of non-cyclic charged variants of B1.
Scheme 5: Partial reduction of compound B1 to B14.
Figure 3: Kirby–Bauer zones of inhibition for all variants B1–B14 compared to original berberine (B). Mean zo...
Scheme 6: Synthesis of the substituted 2-bromoaminonaphthalenes 9 and 10.
Scheme 7: Completion of the synthesis of variants C1–C4.
Figure 4: Kirby–Bauer zones of inhibition for variants C1–C4 compared to original chelerythrine (C). Mean zon...
Figure 5: Effects of original berberine and all variants against T84 human colon cancer cells. Cells were tre...
Figure 6: Effects of original chelerythrine and all variants against T84 human colon cancer. Cells were treat...
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
- installation of the phosphocholine moiety (67%) followed by the deprotection of the secondary alcohol (100%) and its acetylation (53%) produced 13.6. Wissner et al. also reported the incorporation of a gem-dimethyl substituent on the glycerol backbone [97]. One illustration of this structural modification is
- alcohol produced 27.6 that, in a two-step sequence, was used to install the phosphocholine moiety to produce 27.8. The double structural modification of edelfosine that consists to link the lipid chain via a thioether function and to replace the phosphate moiety by a thiophosphate was reported by
Graphical Abstract
Figure 1: Chemical structure of some natural ether lipids (ELs).
Figure 2: Synthesis of lyso-PAF and PAF from 1-O-alkylglycerol [64].
Figure 3: Synthesis of lyso-PAF from 1,3-benzylideneglycerol 3.1 [69].
Figure 4: A) Synthesis of the two enantiomers of octadecylglycerol (4.6 and 4.10) from ᴅ-mannitol (4.1); B) s...
Figure 5: Four-step synthesis of PAF 5.6 from (S)-glycidol [73].
Figure 6: Synthesis of 1-O-alkylglycerol A) from solketal, B) from ᴅ- or ʟ-tartaric acid and the intermediate ...
Figure 7: Synthesis of EL building blocks starting from substituted glycidol 7.1a–c [82].
Figure 8: Synthesis of PAF 8.5 by using phosphoramidite 8.2 [86].
Figure 9: Synthesis of oleyl-PAF 9.7 from ʟ-serine [88].
Figure 10: Synthesis of racemic analogues of lyso-PAF 10.8 and PAF 10.9 featuring a phenyl group between the g...
Figure 11: Synthesis of racemic deoxy-lyso-PAF 11.7 and deoxy-PAF 11.8 [91].
Figure 12: Synthesis of racemic thio-PAF 12.8 [93].
Figure 13: Racemic synthesis of 13.6 to illustrate the modification of the glycerol backbone by adding a methy...
Figure 14: Racemic synthesis of 14.5 as an illustration of the introduction of methyl substituents on the glyc...
Figure 15: Synthesis of functionalized sn-2-acyl chains of PC-EL; A) Steglich esterification or acylation reac...
Figure 16: Synthesis of racemic mc-PAF (16.3), a carbamate analogue of PAF [102].
Figure 17: A) Synthesis of (R)-17.2 and (S)-17.6 starting from (S)-solketal (17.1); B) synthesis of N3-PAF (17...
Figure 18: Modification of the phosphocholine polar head to produce PAF analogues [81].
Figure 19: Racemic PAF analogues 19.3 and 19.5 characterized by the absence of the phosphate group [107].
Figure 20: Synthesis of PIP3-PAF (20.7) [108].
Figure 21: Large-scale synthesis of C18-edelfosine (21.8) [116].
Figure 22: Synthesis of C16-edelfosine (22.10) starting from isopropylidene-ʟ-glyceric acid methyl ester (22.1...
Figure 23: Phosphocholine moiety installation by the use of chlorophosphite 23.2 as key reagent [119].
Figure 24: Synthesis of rac-1-alkyl-2-O-methylglycerol (AMG) [120].
Figure 25: Synthesis of stereocontrolled 1-alkyl-2-O-methyl glycerol 25.9 (AMG) from dimethyl ᴅ-tartrate [81].
Figure 26: A) Racemic synthesis of thioether 26.4 [129,130], B) structure of sulfone analogue 26.5 [129].
Figure 27: Stereocontrolled synthesis of C18-edelfosine thioether analogue 27.8 [118].
Figure 28: Synthesis of thioether 28.4 that include a thiophosphate function [134].
Figure 29: Synthesis of ammonium thioether 29.4 and 29.6 [135].
Figure 30: Synthesis of the N-methylamino analogue of edelfosine 30.6 (BN52211) [138].
Figure 31: Synthesis of 1-desoxy analogues of edelfosine; A) with a saturated alkyl chain; B) synthesis of the...
Figure 32: Stereocontrolled synthesis of edelfosine analogue (S)-32.8 featuring a C18:1 lipid chain [142].
Figure 33: Synthesis of edelfosine analogues with modulation of the lipid chain; A) illustration with the synt...
Figure 34: Synthesis of phospholipid featuring a carbamate function to link the lipid chain to the glycerol un...
Figure 35: Synthesis of sesquiterpene conjugates of phospho glycero ether lipids [148].
Figure 36: Racemic synthesis of methyl-substituted glycerol analogues 36.7 and 36.10: A) synthesis of diether ...
Figure 37: Racemic synthesis of ilmofosine (37.6) [155,156].
Figure 38: A) Stereoselective synthesis of 38.5 via a stereoselective hydroboration reaction; B) synthesis of ...
Figure 39: Racemic synthesis of SRI62-834 (39.6) featuring a spiro-tetrahydrofurane heterocycle in position 2 ...
Figure 40: Racemic synthesis of edelfosine analogue 40.5 featuring an imidazole moiety in sn-2 position [160].
Figure 41: Racemic synthesis of fluorine-functionalized EL: A) Synthesis of 41.6 and B) synthesis of 41.8 [161-163].
Figure 42: A) Synthesis of the β-keto-ester 42.6 that also features a decyl linker between the phosphate and t...
Figure 43: Synthesis of phosphonate-based ether lipids; A) edelfosine phosphonate analogue 43.7 and B) thioeth...
Figure 44: Enantioselective synthesis of phosphonates 44.3 and 44.4 [171].
Figure 45: Racemic synthesis of phosphinate-based ether lipid 45.10 [172].
Figure 46: Racemic synthesis of edelfosine arsonium analogue 46.5 [173].
Figure 47: Synthesis of edelfosine dimethylammonium analogue 47.2 [118].
Figure 48: Synthesis of rac-C18-edelfosine methylammonium analogue 48.4 [176].
Figure 49: A) Synthesis of edelfosine N-methylpyrrolidinium analogue 49.2 or N-methylmorpholinium analogue 49.3...
Figure 50: A) Synthesis of edelfosine’s analogue 50.4 with a PE polar group; B) illustration of a pyridinium d...
Figure 51: A) Synthesis of 51.4 featuring a thiazolium cationic moiety; B) synthesis of thiazolium-based EL 51...
Figure 52: Synthesis of cationic ether lipids 52.3, 52.4 and 52.6 [135,183].
Figure 53: Synthesis of cationic carbamate ether lipid 53.5 [184].
Figure 54: Synthesis of cationic sulfonamide 54.5 [185].
Figure 55: Chemical structure of ONO-6240 (55.1) and SRI-63-119 (55.2).
Figure 56: Synthesis of non-ionic ether lipids 56.2–56.9 [188].
Figure 57: Synthesis of ether lipid conjugated to foscarnet 57.6 [189].
Figure 58: A) Synthesis of ether lipid conjugated to arabinofuranosylcytosine; B) synthesis of AZT conjugated ...
Figure 59: Synthesis of quercetin conjugate to edelfosine [191].
Figure 60: Synthesis of 60.8 (Glc-PAF) [194].
Figure 61: A) Synthesis of amino ether lipid 61.7 functionalized with a rhamnose unit and its amide analogue 6...
Figure 62: A) Synthesis of glucose ether lipid 62.4; B) structure of ether lipid 62.5 possessing a maltose uni...
Figure 63: A) Synthesis of glucuronic methyl ester 63.8; B) structure of cellobiose 63.9 and maltose 63.10 ana...
Figure 64: A) Synthesis of maltosyl glycerolipid 64.7; B) structure of lactose analogue 64.8 prepared followin...
Figure 65: A) Asymmetric synthesis of the aglycone moiety starting from allyl 4-methoxyphenyl ether; B) glycos...
Figure 66: A) Synthesis of ohmline possessing a lactose moiety. B) Structure of other glyco glycero lipids pre...
Figure 67: A) Synthesis of lactose-glycerol ether lipid 67.5; B) analogues possessing a maltose (67.6) or meli...
Figure 68: Synthesis of digalactosyl EL 68.6, A) by using trityl, benzyl and acetyl protecting groups, B) by u...
Figure 69: A) Synthesis of α-ohmline; B) structure of disaccharide ether lipids prepared by using similar meth...
Figure 70: Synthesis of lactose ether lipid 70.3 and its analogue 70.6 featuring a carbamate function as linke...
Figure 71: Synthesis of rhamnopyranoside diether 71.4 [196].
Figure 72: Synthesis of 1-O-hexadecyl-2-O-methyl-3-S-(α-ᴅ-1'-thioglucopyranosyl)-sn-glycerol (72.5) [225].
Figure 73: A) Preparation of lipid intermediate 73.4; B) synthesis of 2-desoxy-C-glycoside 73.10 [226].
Figure 74: Synthesis of galactose-pyridinium salt 74.3 [228].
Figure 75: Synthesis of myo-inositol derivative Ino-C2-PAF (75.10) [230].
Figure 76: A) Synthesis of myo-inositol phosphate building block 76.7; B) synthesis of myo-inositolphosphate d...
Figure 77: A) Synthesis of phosphatidyl-3-desoxy-inositol 77.4; B) synthesis of phosphono-3-desoxyinositol 77.9...
Figure 78: A) Structure of diether phosphatidyl-myo-inositol-3,4-diphosphate 78.1; B) synthesis of phosphatidy...
Figure 79: A) Synthesis of diether-phosphatidyl derivative 79.4 featuring a hydroxymethyl group in place of a ...
Figure 80: Synthesis of Glc-amine-PAF [78].
Figure 81: Synthesis of glucosamine ether lipid 81.4 and its analogues functionalized in position 3 of the ami...
Figure 82: Synthesis of fully deprotected aminoglucoside ether lipid 82.5 [246].
Figure 83: Synthesis of C-aminoglycoside 83.12 using Ramberg–Bäcklund rearrangement as a key step [250].
Figure 84: A) List of the most important glyco lipids and amino glyco lipids included in the study of Arthur a...
Figure 85: Synthesis of mannosamine ether lipid 85.6 [254].
Figure 86: A) Synthesis of glucosamine ether lipids with a non-natural ʟ-glucosamine moiety; B) synthesis of e...
Figure 87: A) Structure of the most efficient anticancer agents 87.1–87.4 featuring a diamino glyco ether lipi...
Figure 88: A) Synthesis of diamino glyco ether lipid 87.4; B) synthesis of bis-glycosylated ether lipid 88.10 [256]....
Figure 89: Synthesis of triamino ether lipid 89.4 [260].
Figure 90: Synthesis of chlorambucil conjugate 90.7 [261].
Figure 91: Three main methods for the preparation of glycerol ether lipid 91.3; A) from solketal and via a tri...
Figure 92: Four different methods for the installation of the phosphocholine polar head group; A) method using...
Figure 93: Illustration of two methods for the installation of saccharides or aminosaccharides; A) O-glycosyla...
Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors
- Grace A. Lowe
Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88
- mediators that can be recycled photo- and electrochemically [45][49]. As illustrated in Figure 5, structural modification of the benzimidazole core alters the redox behavior and allows tuning of the oxidation potential. The benzimidazoles shown all have enough reducing power to reductively quench Ru(bpy)3
Graphical Abstract
Figure 1: Diagram comparing the two reaction pathways for sacrificial electron donors (SD) in photocatalyzed ...
Figure 2: Diagram showing water-splitting systems developed by Girault, Scanlon, and co-workers that employ i...
Figure 3: Diagram illustrating the transfer of electrons in a photocatalytic particulate suspensions Z-scheme...
Figure 4: A. Structures of the molecules represented in part B. The numbers in brackets correspond to the com...
Figure 5: A. Structures of the molecules represented in part B. The numbers in brackets correspond to the com...
Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control
- Carlee A. Montgomery and
- Graham K. Murphy
Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86
- hard fluoride interacts with the stronger σ-hole. Structural modification of the β-dicarbonyl auxiliary has led to improved outcomes, due to increased ylide stability rather than decreasing activation energies of the fluorination reaction. There are, however, other conflicting pieces of evidence that
Graphical Abstract
Figure 1: Generic representation of halogen bonding.
Figure 2: Quantitative evaluation of σ-holes in monovalent iodine-containing compounds; and, qualitative mole...
Figure 3: Quantitative evaluation of σ-holes in hypervalent iodine-containing molecules; and, qualitative MEP...
Figure 4: Quantitative evaluation of σ-holes in iodonium ylides; and, qualitative MEP map of I-12 from −0.083...
Scheme 1: Outline of possible reaction pathways between iodonium ylides and Lewis basic nucleophiles (top); a...
Scheme 2: Metal-free cyclopropanations of iodonium ylides, either as intermolecular (a) or intramolecular pro...
Figure 5: Zwitterionic mechanism for intramolecular cyclopropanation of iodonium ylides (left); and, stepwise...
Scheme 3: Metal-free intramolecular cyclopropanation of iodonium ylides.
Figure 6: Concerted cycloaddition pathway for the metal-free, intramolecular cyclopropanation of iodonium yli...
Scheme 4: Reaction of ylide 6 with diphenylketene to form lactone 24 and 25.
Figure 7: Nucleophilic (top) and electrophilic (bottom) addition pathways proposed by Koser and Hadjiarapoglo...
Scheme 5: Indoline synthesis from acyclic iodonium ylide 31 and tertiary amines.
Scheme 6: N-Heterocycle synthesis from acyclic iodonium ylide 31 and secondary amines.
Figure 8: Proposed mechanism for the formation of 33a from iodonium ylides and amines, involving an initial h...
Scheme 7: Indoline synthesis from acyclic iodonium ylides 39 and tertiary amines under blue light photocataly...
Scheme 8: Metal-free cycloproponation of iodonium ylides under blue LED irradiation. aUsing trans-β-methylsty...
Figure 9: Proposed mechanism of the cyclopropanation between iodonium ylides and alkenes under blue LED irrad...
Scheme 9: Formal C–H alkylation of iodonium ylides by nucleophilic heterocycles under blue LED irradiation.
Figure 10: Proposed mechanism of the formal C–H insertion of pyrrole under blue LED irradiation.
Scheme 10: X–H insertions between iodonium ylides and carboxylic acids, phenols and thiophenols.
Figure 11: Mechanistic proposal for the X–H insertion reactions of iodonium ylides.
Scheme 11: Radiofluorination of biphenyl using iodonium ylides 54a–e derived from various β-dicarbonyl auxilia...
Scheme 12: Radiofluorination of arenes using spirocycle-derived iodonium ylides 56.
Scheme 13: Radiofluorination of arenes using SPIAd-derived iodonium ylides 58.
Figure 12: Calculated reaction coordinate for the radiofluorination of iodonium ylide 60.
Scheme 14: Radiofluorination of iodonium ylides possessing various ortho- and para-substituents on the iodoare...
Figure 13: Difference in Gibbs activation energy for ortho- or para-anisyl derived iodonium ylides 63a and 63b....
Figure 14: Proposed equilibration of intermediates to transit between 64a (the initial adduct formed between 6...
Scheme 15: Comparison of 31 and ortho-methoxy iodonium ylide 39 in rhodium-catalyzed cyclopropanation and cycl...
Figure 15: X-ray crystal structure of dimeric 39 [6], (CCDC# 893474) [143,144].
Scheme 16: Enaminone synthesis using diazonium and iodonium ylides.
Figure 16: Transition state calculations for enaminone synthesis from iodonium ylides and thioamides.
Scheme 17: The reaction between ylides 73a–f and N-methylpyrrole under 365 nm UV irradiation.
Figure 17: Crystal structures of 76c (top) and 76e (bottom) [101], (CCDC# 2104180 & 2104181) [143,144].
The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban
- Martin Vrbický,
- Karel Macek,
- Jaroslav Pochobradský,
- Jan Svoboda,
- Miloš Sedlák and
- Pavel Drabina
Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46
- 15 and 19 was also performed with the aim to increase the enantiomeric purity of the corresponding nitroaldol products 21–26. The structural modification consisted in the introduction of different alkyl moieties to the carbamate functional group of the aldehyde intermediates 15–20. As bulky and/or
- 2). The bulky (R2 = t-Bu) or chiral (R2 = ʟ-menthyl or (−)-bornyl) alkoxy groups (derived from relatively inexpensive and readily available alcohols) were introduced into the carbamate moiety instead of an ethyl group as in aldehydes 15 and 19. Here, the influence of this structural modification of
Graphical Abstract
Figure 1: The structure of the oxazolidine-2-one-containing drugs linezolid (1) and rivaroxaban (2).
Figure 2: Overview of the chiral ligands that were used for the study of the asymmetric Henry reaction.
Scheme 1: Syntheses of aldehydes 15–20.
Scheme 2: Synthesis of linezolid (1) and rivaroxaban (2) from nitroaldols 24 or 26.
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
- Umesh P. Aher,
- Dhananjai Srivastava,
- Girij P. Singh and
- Jayashree B. S
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
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
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...
Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions
- Shrikant D. Tambe,
- Kwan Hong Min,
- Naeem Iqbal and
- Eun Jin Cho
Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114
- hypothesized that the structural modification of the substrate might affect its reactivity, and to our delight, the introduction of an ortho-phenyl moiety on the N-benzylideneaniline species provided the desired 1,2-diamine product, wherein the N,N-dicyclohexylmethylamine (Cy2NMe) acted as both the coupling
Graphical Abstract
Scheme 1: Photocatalytic transformations of imines.
Scheme 2: Substrate scope for the radical cross-couplings. Reaction conditions: 1 (0.3 mmol), under argon atm...
Scheme 3: Substrate scope for the homocoupling. Reaction conditions: 1 (0.3 mmol), under argon atmosphere, is...
Scheme 4: Reduction of the imine 1a to the amine 4a.
Scheme 5: Proposed mechanism.
Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors
- Abimelek Cortes-Pacheco,
- María Adelina Jiménez-Arellanes,
- Francisco José Palacios-Can,
- José Antonio Valcarcel-Gamiño,
- Rodrigo Said Razo-Hernández,
- María del Carmen Juárez-Vázquez,
- Adolfo López-Torres and
- Oscar Abelardo Ramírez-Marroquín
Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108
- approximation, to study the effect of these structural modification on the pharmacodynamics, we performed a molecular docking over two MPPs. In Table 4, the interaction energy value (MolDock Score) [38] of each compound with the two different MMPs obtained from the docking calculation is displayed. Also, the
Graphical Abstract
Figure 1: Previously reported antiinflammatory bisphosphonates 1 and 2. edema inhibition (in %, carrageenan m...
Figure 2: Designed bisphosphonic esters as antiinflammatory agents.
Scheme 1: Synthesis of the intermediate bromoaceto esters 7–10.
Scheme 2: Synthesis of the bisphosphonates 3–6.
Figure 3: Coordination of the Zn2+ ion by residues and by the carbonyl ester oxygen atom of molecule 3. The b...
Figure 4: 2D schematic representations of the MMP-8 catalytic site, with 3–6 and the most relevant interactio...
Figure 5: 2D schematic representations of the MMP-9 catalytic site, with 3–6 and the most relevant interactio...
Development of fluorinated benzils and bisbenzils as room-temperature phosphorescent molecules
- Shigeyuki Yamada,
- Takuya Higashida,
- Yizhou Wang,
- Masato Morita,
- Takuya Hosokai,
- Kaveendra Maduwantha,
- Kaveenga Rasika Koswattage and
- Tsutomu Konno
Beilstein J. Org. Chem. 2020, 16, 1154–1162, doi:10.3762/bjoc.16.102
- (Figure 2A), which show prominent fluorescence not only in dilute solution, but also in the crystalline state [27][28][29][30][31]. As a powerful tool to develop novel pure organic phosphorescent molecules, we envisioned the structural modification of the carbon–carbon triple (C≡C) bond in fluorinated
- effects of structural modification (i.e., the benzil structure with a tolane vs bisbenzil moiety) and incorporation of fluorine atoms on the phosphorescence, the ratio between the peak intensities at ≈395 and ≈560 nm (I560/I395) was quantitatively calculated, and the results are summarized in Table 1. The
Graphical Abstract
Figure 1: (A) Transition-metal-containing and (B) pure organic phosphorescent materials reported thus far (bp...
Figure 2: (A) Chemical structures of fluorescent bistolane derivatives previously developed by our group and ...
Scheme 1: Synthetic pathway for fluorinated benzil (2) and bisbenzil (3) derivatives.
Scheme 2: Proposed mechanism of Pd(II)-catalyzed alkyne oxidation by dimethyl sulfoxide (DMSO).
Figure 3: Mulliken charge distributions of fluorinated 1a and nonfluorinated 1c obtained from density functio...
Figure 4: Absorption and photoluminescence (PL) spectra of (A) 2a, (B) 2b, (C) 3a, (D) 3b, and (E) 3c in tolu...
Figure 5: Distributions of molecular orbitals (isosurface value: 0.04 a.u.) involved in vertical electronic t...
Synthesis of 9-O-arylated berberines via copper-catalyzed CAr–O coupling reactions
- Qiaoqiao Teng,
- Xinhui Zhu,
- Qianqian Guo,
- Weihua Jiang,
- Jiang Liu and
- Qi Meng
Beilstein J. Org. Chem. 2019, 15, 1575–1580, doi:10.3762/bjoc.15.161
- 9-O-phenylene-bridged berberine dimer (5) was synthesized by copper-catalyzed cross-coupling of tetrahydroberberrubine and aryl iodides, followed by oxidation with I2. Keywords: arylation; berberines; cross-coupling; copper; lipophilicity; structural modification; Introduction Berberine (BBR) is a
Graphical Abstract
Scheme 1: Synthetic pathway of 9-O-R BBR.
Scheme 2: Resonance of berberrubine leading to the failure of direct BBRB cross coupling.
Scheme 3: 9-O-Aryl berberine scope via cross-coupling reaction.
Scheme 4: 9-O-Ph-linked berberine dimer through double cross-coupling reaction.
Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce
- Hidekazu Komatsu,
- Takashi Shirakawa,
- Takeo Uchiyama and
- Tsutomu Hoshino
Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27
- treatment had no activity, supporting that a macrocyclic peptide would be essential for biological activity. The sequence Z-dhThr17-D-alloThr18 of cichorinotoxin was converted to Z-dhThr17-E-dhThr18 by alkaline hydrolysis. This additional structural modification may have further decreased the activity
Graphical Abstract
Figure 1: FABMS spectrum (positive mode, NBA matrix) of cichorinotoxin over the mass range of m/z 150─1000.
Figure 2: The segment identified based on the FABMS spectrum (peptide fragment b ions).
Figure 3: NMR analyses of the segment consisting of 3-hydroxydecanoyl-dehydrothreonin-proline (600 MHz, aceto...
Figure 4: Key NMR observations used to construct the backbone sequence.
Figure 5: Fragment obtained by acid hydrolysis and each amino acid was exclusively D-configuration (peptide f...
Figure 6: The complete structure of cichorinotoxin monoacetate and the assignments of 1H NMR chemical shifts,...
Figure 7: Determination of the positions of the acetyl groups in the tetraacetate.
Figure 8: Partial structure of compound A as deduced from its NOE data; key NOEs are represented by double-he...
Figure 9: Partial structure of compound B (Val16 to Val22 residues). The chemical shifts (δH and δC (ppm)) ar...
Figure 10: Mechanism of the formation of compounds A and B from cichorinotoxin by alkaline hydrolysis.
Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues
- Kai Zhang,
- Jiarong Li,
- Honglin Liu,
- Haiyou Wang and
- Lamusi A
Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207
- as the glycosylation donor of C9–OH, but also the protecting group of C17–OH, greatly reducing the synthetic steps and costs. Macrolide compounds are a new kind of insecticides and fungicides which have also been widely applied in medicine [14][15]. Currently, research on structural modification of
Graphical Abstract
Figure 1: Structures of spinosad and spinetoram.
Scheme 1: Comparison of previous synthesis and self-protection synthesis.
Scheme 2: Synthesis of spinetoram J from spinosyn A based on a self-protection strategy.
Scheme 3: Synthesis of spinetoram J analogues.
Functionalization of graphene: does the organic chemistry matter?
- Artur Kasprzak,
- Agnieszka Zuchowska and
- Magdalena Poplawska
Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177
- effects and to open new avenues for the application of GO and RGO, a chemical functionalization was conducted [9][10][11][12]. There are two approaches for the structural modification of GO and RGO: (i) the reaction of oxygen-bearing groups or (ii) the functionalization of sp2 carbons from the graphene
- functionalization of the graphene-family material. In fact, the structural modification of GO and RGO constitutes a key starting point of such research. Even though many studies on chemical functionalization have presented very interesting and novel applications of GO and RGO derivatives they also present yet
Graphical Abstract
Figure 1: Partial structure [7,8] of the (a) graphene oxide (GO) and (b) reduced graphene oxide (RGO).
Figure 2: Mechanism of the amidation/esterification-type reactions with the GO/RGO using carbodiimide and N-h...
Figure 3: Mechanism of the Steglich esterification with the GO/RGO: (a) acid–base reaction of the carboxyl gr...
Figure 4: Mechanism of the epoxide ring opening reaction with the GO/RGO.
Figure 5: Generation of the free amine (nucleophile) from the corresponding amine hydrohalide using an acid–b...
Figure 6: Mechanism of amidation/esterification-type reactions with the GO/RGO using 1,1’-carbonyldiimidazole...
Figure 7: Mechanism of the covalent functionalization of graphene-family material applying diazonium salts ch...
Recent advances in phosphorescent platinum complexes for organic light-emitting diodes
- Cristina Cebrián and
- Matteo Mauro
Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124
- between hundreds of nanoseconds to several microseconds, constituting a formally spin-forbidden transition (phosphorescence). Structural modification of the TMCs and proper tailoring of coordinated ligands can independently act on the nature, energy and topology of frontier orbitals. In fact, a fine
Graphical Abstract
Figure 1: Molecular structure of neutral platinum(II) complex 1 bearing four monodentate ligands; cy = cycloh...
Figure 2: Chemical structure of the dinuclear Pt complexes 2a–b and 3 [20].
Figure 3: Molecular structure of platinum(II) complexes bearing isoquinolinylpyrazolates; dip = 2,6-diisoprop...
Figure 4: Selected neutral platinum(II) complexes featuring dianionic biazolate and neutral bipyridines [27].
Figure 5: Selected neutral platinum(II) complexes from bipyrazolate and carbene-based chelates [34,35].
Figure 6: Cyclometalated thiazol-2-ylidene platinum(II) complexes with different acetylacetonate ligands [37].
Figure 7: Neutral platinum(II) complexes 13–15 bearing azolate ligands [13].
Figure 8: Chemical structure of neutral platinum(II) complexes 16–18 bearing azine-pyrazolato bidentate ligan...
Figure 9: Molecular structure of carbene-containing cyclometallated alkynylplatinum(II) complexes 19–21 [41].
Figure 10: Chemical structure of platinum(II) complexes 22a–d bearing asymmetric C^N^N tridentate ligands [53].
Figure 11: Chemical structure of platinum(II) complexes 23 bearing bis-cyclometalating 2,6-dipyridylbenzene ty...
Figure 12: Molecular structure of dendritic carbazole-containing alkynyl-platinum(II) complexes 24a–d [62].
Figure 13: Molecular structure of bipolar alkynyl-platinum(II) complexes 25 bearing carbazole and electron-acc...
Figure 14: Molecular structures of neutral platinum(II) complexes comprising donor-acceptor alkynyls (26) or e...
Figure 15: Chemical structure of the asymmetric Pt(II) derivatives 28 bearing triazole and tetrazole moieties ...
Figure 16: Molecular structure of the tetradentate platinum complexes 29–32 bearing N^C^C^N and C^C^C^N ligand...
Figure 17: Chemical structure of the tetradentate Pt complexes 33–38 based on N^C^C^N-type of ligands [80-84].
Figure 18: Chemical structure of the macrocyclic tetradentate platinum complexes reported by Wang and co-worke...
Figure 19: Molecular structure of complex 41–46 [88,89].
Figure 20: Molecular structure of asymmetric derivatives 47–49 based on triaryl-type of bridge [90].
Figure 21: Chemical structure of the asymmetric tetradentate derivatives 50 and 51 based on spirofluorene link...
Figure 22: Molecular structure of the pyridylazolate-based complexes 52–54 reported by Chi and co-workers [97].
Figure 23: Chemical structure of the red-to-NIR emitting complexes 55–57 bearing donor–acceptor triphenylamino...
Figure 24: Molecular structures of the Pt(IV) derivatives 58 and 59 employed as triplet emitters in solution-p...
Synthesis of fluoro-functionalized diaryl-λ3-iodonium salts and their cytotoxicity against human lymphoma U937 cells
- Prajwalita Das,
- Etsuko Tokunaga,
- Hidehiko Akiyama,
- Hiroki Doi,
- Norimichi Saito and
- Norio Shibata
Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24
- suggested that antitumor drug candidates could be designed by further structural modification of these compounds 3. Moreover, with 3p exhibiting the greatest potency against U937 cells with comparably lower toxicity against AGLCL cells, further biological studies using 3p including in vivo evaluation should
Graphical Abstract
Figure 1: Compounds used for the biological study.
Figure 2: Compounds 1–4 induced cell death in U937 cells. Briefly, U937 cells (1 × 104 cells/mL) were incubat...
Scheme 1: Synthesis of pentafluoro-(2-iodophenyl)-λ6-sulfane (7).
Scheme 2: Synthesis of unsymmetrical ortho-SF5 diaryliodonium salts 3p, 4b, 5a and 6a.
Figure 3: X-ray crystallographic structure of 3p drawn at 50% probability (CCDC 1573953).
Figure 4: Ortho-SF5 phenyl iodonium salts 3p and 5a and their structural components 7 and 9 induced cell deat...
Figure 5: 3k, 3m and 3p induced cell death in AGLCL, a human normal B cell line. Briefly, AGLCL cells (1 × 104...
Mechanochemical synthesis of thioureas, ureas and guanidines
- Vjekoslav Štrukil
Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178
- Cs2CO3 for 3 hours finally afforded phenytoin in an excellent 84% isolated yield (Scheme 16c). The introduction of a sulfonyl group on the urea framework has been found to be the crucial structural modification in the development of the 1st generation antidiabetic drugs such as tolbutamide and
Graphical Abstract
Scheme 1: a) Schematic representations of unsubstituted urea, thiourea and guanidine. b) Wöhler's synthesis o...
Figure 1: Antidiabetic (1–3) and antimalarial (4) drugs derived from ureas and guanidines currently available...
Scheme 2: The structures of some representative (thio)urea and guanidine organocatalysts 5–8 and anion sensor...
Scheme 3: Solid-state reactivity of isothiocyanates reported by Kaupp [30].
Scheme 4: a) Mechanochemical synthesis of aromatic and aliphatic di- and trisubstituted thioureas by click-co...
Figure 2: The supramolecular level of organization of thioureas in the solid-state.
Figure 3: The supramolecular level of organization of thioureas in the solid-state.
Scheme 5: Thiourea-based organocatalysts and anion sensors obtained by click-mechanochemical synthesis.
Scheme 6: Mechanochemical desymmetrization of ortho-phenylenediamine.
Scheme 7: Mechanochemical desymmetrization of para-phenylenediamine.
Scheme 8: a) Selected examples of a mechanochemical synthesis of aromatic isothiocyanates from anilines. b) O...
Scheme 9: In solution, aromatic N-thiocarbamoyl benzotriazoles 27 are unstable and decompose to isothiocyanat...
Scheme 10: Mechanosynthesis of a) bis-thiocarbamoyl benzotriazole 29 and b) benzimidazole thione 31. c) Synthe...
Figure 4: In situ Raman spectroscopy monitoring the synthesis of thiourea 28d in the solid-state. N-Thiocarba...
Scheme 11: a) The proposed synthesis of monosubstituted thioureas 32. b) Conversion of N-thiocarbamoyl benzotr...
Scheme 12: A few examples of mechanochemical amination of thiocarbamoyl benzotriazoles by in situ generated am...
Scheme 13: Mechanochemical synthesis of a) anion binding urea 33 by amine-isocyanate coupling and b) dialkylur...
Scheme 14: a) Solvent-free milling synthesis of the bis-urea anion sensor 35. b) Non-selective desymmetrizatio...
Scheme 15: a) HOMO−1 contours of mono-thiourea 19b and mono-urea 36. b) Mechanochemical synthesis of hybrid ur...
Scheme 16: Synthesis of ureido derivatives 38 and 39 from KOCN and hydrochloride salts of a) L-phenylalanine m...
Scheme 17: a) K2CO3-assisted synthesis of sulfonyl (thio)ureas. b) CuCl-catalyzed solid-state synthesis of sul...
Scheme 18: Two-step mechanochemical synthesis of the antidiabetic drug glibenclamide (2).
Scheme 19: Derivatization of saccharin by mechanochemical CuCl-catalyzed addition of isocyanates.
Scheme 20: a) Unsuccessful coupling of p-toluenesulfonamide and DCC in solution and by neat/LAG ball milling. ...
Scheme 21: a) Expansion of the saccharin ring by mechanochemical insertion of carbodiimides. b) Insertion of D...
Scheme 22: Synthesis of highly basic biguanides by ball milling.
