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

• digest and metabolic processes [3]. Furthermore, cyclization generally helps to fix the active conformation of a peptide needed to interact with the respective cellular target. Incorporation of non-proteinogenic and unusual amino acids often is related to their biological function. For example, trapoxin

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• conformation. The 1,2-oxazole rings occupy equatorial positions at the 2nd atom of the piperidinium ring, and the dihedral angle H(10)–C(10)–C(5)–O(1) is 158°. The methoxycarbonyl group is in the same plane as the 1,2-oxazole ring. The bond lengths and angles of 1,2-oxazole rings are shown in Table 1 which

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• seen that the conformation is quite appropriate for the formation of lactone 10. The hydrogen bond between the C=O group of methoxy ester and NH group of the carbamate in 7 provides an appropriate conformation for the formation of lactone 10. Additionally, according to the conformational analysis of

• . Our computations demonstrate that the formation of the five-membered lactone is kinetically more favourable, and the formation of six-membered lactone is not feasible under the experimental conditions. The conformation of epoxide 7 is quite appropriate for the formation of the five-membered lactone 10

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

• - instead of 7-bromotryptophan yielded the expected stapled peptide P1a. Next, the secondary structures of the two stapled peptides P1a and P1b were investigated by CD spectroscopy. Unfortunately, both peptides did not show enhanced helical conformation in water. To get more information about the structure

• additional ethylene unit in the linker suggested a conformation with the highest similarity to the linear reference peptide P6 (see Supporting Information File 1), thus representing a good compromise between rigidity and preservation of the target secondary structure. Serine in i-position and glutamic acid

• peptide (i.e., a cumulative total of 10.5 μs per peptide) performed with the ff14SB/GAFF [90][91] and TIP4Pew [91] force field parameters for the peptides and water, respectively, as well as specifically derived parameters for non-standard residues of the linker in stapled peptide P5. The conformation of

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

• HQ[n]s with that of Q[n]s, Buschmann [26] observed that HQ[6] 2 (Scheme 1) formed complexes only with Ni2+, Co2+, and UO22+ with extremely low affinity, which may be caused by the poor solubility of HQ[6] 2 in aqueous solution and its universal “alternate” conformation. Most modified

• X-ray diffraction analysis. As shown in Figure 1, the nitrobenzene-containing hemicucurbituril 9 adopted a square-cavity conformation. Notably, three nitrobenzene units shared nearly a plane. It should be highlighted that macrocycle 9 gave concise proton and carbon signals in the 1H and 13C NMR

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• , C. tropicalis, and C. glabrata standard strains. A deep conformational survey was monitored using DFT calculations with the aim to explain the importance of the final conformation in the biological experimental results. Keywords: antituberculosis; bidentate ligands; DFT; nickel; palladium

• activities in relation to the tested microorganisms together depending on the type of synthesized compounds. In general, the most active compound was the L3-Ni complex possessing the indole ring has a single conformation (detected by 1H NMR spectroscopy and confirmed by DFT calculations), which corresponded

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• class 3 atropisomers under protic and aprotic conditions due to a strong intramolecular N–H–O hydrogen bond that locks one of the axes into a planar conformation and proposed that the quinoid-nitrogen axis exists in a planar exo conformation [97]. 4. Enantioselective synthesis of axially chiral allenes

GlycoBioinformatics

• Kiyoko F. Aoki-Kinoshita,
• Frédérique Lisacek,
• Niclas Karlsson,
• Daniel Kolarich and
• Nicolle H. Packer

Beilstein J. Org. Chem. 2021, 17, 2726–2728, doi:10.3762/bjoc.17.184

• article by Barnett et al. [2] uses molecular dynamics to show that O-linked glycosylation alters peptide conformation, which influences the binding of the peptides to antibodies, despite the fact that glycans are not directly involved in the binding. Another molecular modeling article by Fogarty et al. [3

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

• reactions, along with recent new promoter-dependent advances. It is generally agreed that the stereochemical outcome of glycosylation can be affected by multiple factors [66][67][68][69], which include i) structure and conformation of the glycosyl substrates, ii) glycosylation reagents or promoters, iii

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• synthases seem to be quite random, only the active site is lined with mostly non-polar residues. They contour the active site and force the substrate into a certain conformation which, after substrate ionisation, determines the reaction pathway that is taken by the cationic cascade. Here we present site

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

• enantioselectivity, but the catalyst itself accommodates the anion by adopting a helical conformation upon complexation (Scheme 18a) [84][85][86]. Initial studies proved these systems highly effective for the enantioselective Reissert reaction of quinolines with silyl ketene acetals [22], which could be later

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• critical solution temperature. In the case of a polymer with a UCST, the polymer is in a phase-separated, collapsed state below this temperature. Heating increases the solubility until only one phase is present above the UCST. Schematically, the chains are in stretched conformation and soluble in all

• switch between a stretched and a collapsed brush conformation, leading to a change in macroscopic properties, such as contact angle or layer thickness, in contrast to the cloud point for free polymer chains. The influence of covalent bonding on a flat or curved surface will be considered using the

• distance between the anchor points is smaller than the undisturbed gyration radius Rg of the free chains, the polymer chains stretch to the so-called polymer brush conformation, due to the repulsive segment–segment interaction, in contrast to the so called “mushroom regime”. That means, the intermolecular

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

• , fluorine, and carboxymethyl groups, prevented the formation of insoluble aggregates by disrupting hydrogen-bond networks. Dramatic differences in the conformation (e.g., radius of gyration and glycosidic bond conformation) and aggregation behaviour (i.e., crystallinity and solubility) were observed for

• that, for some residues, the 4,6-O-benzylidene group stabilizes a boat conformation (1,4B or B2,5), in contrast to the standard chair (4C1). This unexpected conformation did not affect the stereoselectivity of the glycosylation, permitting the preparation of linear β(1–3)-glucans of different lengths

• ]. The replacement of a single Glc unit with a Man unit was sufficient to disrupt this secondary structure and significantly increased the isolated yield of the final compounds. Molecular dynamic (MD) simulations predicted a compact helical conformation for the fully deprotected compound, confirmed by

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• ’-position (Table 5). Interestingly the resulting nucleotides were found to adopt a conformation which was, with respect to duplex stability, tolerated at terminal positions but not at internal positions [91]. The modified PS-ASOs were transfected into human-607B melanoma cells, and after 48 h, the B-cell

• increased target binding affinity is usually seen relative to modifications on the furanose ring (minor groove). However, when the 2’-amino-LNA scaffolds is used, a very high duplex stability is seen irrespectively of the target (DNA or RNA), as a synergistic effect between the locked sugar conformation and

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• highly complex peptides. Cyclic peptides are known to be structurally and chemically stable against enzymatic degradation because the cyclic skeleton restricts the conformation and limits β-turns. In this manganese catalysis, the late-stage C–H allylation manifold was extended to the construction of a

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• resembled the B- and A-form conformations of natural nucleic acids. The PNA–RNA duplex adopted a conformation very close to the standard A-form helix [40]. In contrast, the PNA–DNA duplex adopted an intermediate structure where positioning of the base pairs was A-like, while the backbone curvature, sugar

• conformation (C2′-endo), base pair inclination, and helical rise resembled B-DNA [39]. The first X-ray crystal structure of a PNA–DNA–PNA triplex revealed a previously unknown helix with a wide diameter of ≈26 Å (compared to 20 Å for A-form duplex) and a wide and deep major groove (Figure 3), given the name "P

• PNA was able to adopt to the conformations of DNA and RNA to some extent, the P-form was the naturally preferred helical conformation of PNA. PNA backbone modifications PNA design was originally assisted by simple computer modeling that replaced the phosphodiester backbone of DNA with pseudopeptide

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• ), compared to data observed previously for mannuronate ester (δH = 4.54 ppm) and hydroxamate (δH = 4.56 ppm) motifs [11]. Finally, the coupling constant calculated for H5 (3JH5-H4 = 8.9 Hz), indicated a solution-phase 4C1 pyranose conformation for newly formed 5. To explore improving the efficiency of the

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• . In the cyclohexadienone cyclophane 6, with its extra sp3-hybridized atom to the bridge, the distortion is reduced, the angle between the planes is just 7°. The conformation of the nitro group has changed. In the absence of a hydroxy group for hydrogen bonding, there is a repulsion between the nitro

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• was also able to fully block CB1 receptor activation (IC50 value of 5.22 ± 0.68 µM). Our results indicate that the new DIM derivatives act as potent CB1 receptor antagonists with inverse agonistic activity, i.e., they stabilize the inactive receptor conformation. Further optimization is warranted

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• due to the 3′-endo conformation which placed the 2′-substituent towards the minor groove rather than to the duplex core [35]. Vilarrasa and co-workers [47] synthesized 2′-uracil-1-yl and 2′-thymin-1-yl derivatives of 2′-deoxythymidine starting from uridine (16). The synthesis started with the TIPDS

• ][31][65]. Bicyclic double-headed nucleosides In this section we have included the double-headed nucleoside monomers, which have a locked nucleic acid type conformation and the additional nucleobase is attached at one of the carbon or nitrogen atoms constituting the bridge (Figure 1). All examples

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

• CSD. In this study we have used the Hirshfeld fingerprint plots together with normal-coordinate structural decomposition and determined crystal structures to elucidate the conformation, present intermolecular interactions, and compare respective contacts within the crystalline architectures

• we were able to deduce the impact a meso halogen has on a porphyrin, for example, meso-halogenation is dependent on the type of alternate substituents present when forming supramolecular assemblies. Furthermore, we have designed a method to predict the conformation of halogenated porphyrins, without

• [18], the conformation of the porphyrin core can play a key role in the binding of small molecules or on its efficiency as an organocatalyst as demonstrated by Roucan et al. [19]. With the continuing interest in nonplanar porphyrins [20] and their relevance for the in vivo functioning of porphyrin

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• arrangement of the sulfinyl group is the most stable conformation of the imine, due to the contribution of the hydrogen bonding of the oxygen and the iminic hydrogen. In this scenario, the tribromomethyl anion attacked the less hindered Re face of the imine with (RS) configuration (Scheme 6). The

• generated, taking place a diastereoselective nucleophilic dichloromethylation of the imine. The addition took place almost exclusively to the Re face of the imine (RS)-14, which is the less sterically hindered in the most stable s-cis conformation (see Scheme 2). The second intramolecular N-alkylation step

• chair-like transition state model with the indium coordinated to the nitrogen atom of the imine, and the sulfinyl and R groups located at axial positions, in a kind of s-cis conformation, was proposed to rationalize the stereochemical outcome. By considering this working model, the nucleophilic attack

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• ᴅ-galacto configuration for all fluoro analogs 59–72. The values of the coupling constants correlated with the 4C1 conformation adopted by the target fluoro analogs in solution (Table 1 and Table S1 in Supporting Information File 1). For example, the magnitude of the germinal fluorine–carbon

• (3JH3/H5-F = 25.5–30.3 Hz) or equatorial (3JH3-F4 = 14.8–16.8 Hz, 3JH5-F4 = 2.5–4.8 Hz) position of the C4 fluorine substituent [57]. Moreover, evaluation of 3JH5-F6 coupling constants revealed that 6-fluoro ᴅ-gluco analogs 59, 62, 64, and 71 assumed preferentially gauche,gauche (gg) conformation of the

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• shift of the equilibrium between the [3 + 1] conformer, related to the shoulder at 255 nm [59], and the basket-type conformation of 22AG, assigned to the positive signal at 290 nm and the weak negative band at 260 nm [60][61] in favor of the latter. Hence, these observations showed that the ligands bind

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• ion intermediate in a stereoselective manner for THP ring formation as shown in Scheme 3. The outcome of exclusive cis-stereoselectivity in the Prins cyclization might be attributed to the most favorable conformation adopted by 12 with equatorial orientation of the 2,6-substituents (R1 and R2). Alder

• presence of the mild Lewis acid InCl3 and benzaldehyde (88), which produced all-cis-tetrahydropyran-4-one 90 in excellent yield. The transformation proceeded through cyclization of a diequatorial chair-like conformation of the oxocarbenium ion 89 to provide an N-acyliminium ion, which upon hydrolysis

• mixture of cis- and trans-220 (dr = 4.1:1.0). It was explained that the diastereoselectivity of the product depends on the size of the substituent. For example, when the substituent is sterically small, it occupies the pseudoaxial position in the reactive conformation 218 (Scheme 52). Li et al. utilized