Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• rapid epimerization during cinnamate hydrolysis. Later, in 2013 Pereda-Miranda and co-workers isolated ten compounds, namely brevipolides A–J (1–10), from the aerial part of Hyptis brevipes Poit. collected in Mexico [12]. The C6’S configuration was then determined by X-ray crystallographic data of the

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

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

• adjacent directing group (see 31h). This manganese(I)-catalyzed late-stage glycosylation provides hexaglycopeptide conjugate 31m without epimerization. Moreover, the late-stage C–H diversification process enabled bioorthogonal access to glycosylated peptides, such as a fluorescent BODIPY-labeled tryptophan

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• CSGALNACT2, which is preferred for synthesizing disaccharide repeats. CHSY1, CHSY3, CHPF, and CHPF2 all exhibit dual β1-3GlcAT and β1-4GlcAT activity. Additional enzymes mediate sulfation. Epimerization of glucuronic acid to iduronic acid by DSE and DSEL results in the conversion of chondroitin sulfates to

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• ratio = 79:21) in 70% yield (Scheme 9). With regard to the partial epimerization of product 21, it may be due to the action of pyridine. In the preparation of compound 21, pyridine is used both as solvent and the acid acceptor. Because pyridine itself can show nucleophilic reactivity in addition to

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• , followed by hydrolysis with solid K2CO3 and water for 30 min (Scheme 5). The desired aldehyde 18 was recovered in an excellent yield of 99%, and product epimerization was not detected based on 13C NMR spectroscopic analysis. This was confirmed by analysis of the 13C chemical shifts of the acetonide group

• starting material was recovered. Use of PCC resulted in product epimerization and so the method was abandoned. Success was achieved by use of IBX in DMSO, overnight, resulting in the recovery of a quantitative yield of 23 (Scheme 6). The amine was synthesized by first converting the primary alcohol to a

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

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

• (Scheme 20). It is important to highlight that cyclization occurred without epimerization with such as strong base. Isoindolines with substituents at 1 and 3 positions were synthesized from an aromatic N-tert-butanesulfinyl imine 67, bearing a Michael acceptor in the ortho-position. Fustero, Barrio and co

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

• ) [63][64]. It was noticed that the problem associated with epimerization of the substrate has been successfully overcome in this reaction, which was demonstrated in the enantioselective total synthesis of (−)-centrolobine using catalytic InBr3 as a mild Lewis acid. This strategy was further explored to

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• , six or eight diastereomers (vide supra) and the analysis and further application of such diastereomeric mixtures is problematic. To improve the diastereomeric ratio and to establish the relative configuration, lactam mixtures 12 were subjected to epimerization at C3 (Table 4). Indeed, 50 mol % KOt-Bu

• ratio of lactam 12f with a quaternary center at C4 did not change at all, neither at room temperature nor at 50 °C (Table 4, entry 6). Lactam 12g with a benzyl group as well as pyrrolidones 12i–k bearing branched 1-arylethyl groups on the nitrogen required warming to 50 °C to induce epimerization at C3

• diastereomeric ratios. To confirm enolate formation, lactam 12f was deprotonated by LDA at −78 °C and quenched with D2O, resulting in lactam 12f with 86% deuterium incorporation, but no change in the diastereomeric ratio. Spirolactams 12m,n were also subjected to epimerization (Scheme 4). The change of the

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• by a dipolar resonance structure containing the 2-fluoroallyl cation and fluoride anion (Scheme 39). A subsequent comparison of the rates of racemization with those of epimerization confirmed experimentally the preference for coupled disrotatory motions in the opening and closing of 2,3-dialkyl-1,1

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• ) catalyst and subsequent base-promoted epimerization produced meloscine (158) in 83% yield. In 2017, Yang and co-workers disclosed the synthesis of (−)-pavidolide B (166) by using a thiyl-radical-mediated [3 + 2] annulation reaction to create four contiguous stereocenters on tricycle 162 in one step [71][72

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• epimerization is required. The requirement of additional reaction steps may explain the lower yield (31%) of this reaction. Note, that from the other three substrates, the product (rac)-27 was obtained in a yield of 52–54%. Since the enolate (rac)-T9 is all-equatorial, and consequently, the energy is lower than

• that of the corresponding stereoisomers, it is more likely that the epimerization occurs after the formation of (rac)-T10. Concerning (rac)-8a and 8b as well as (rac)-11a and 11b, the reagent preference was exactly the opposite: DBU in THF under reflux was effective, while t-BuOK in THF under reflux

• for the formation can be written only from the imides (rac)-11a,b. Apparently, the first step involves a base-catalyzed epimerization into a less-strained cis-annelated system, which undergoes ring inversion, enabling the large halogen atom to be equatorial. This is followed by a deprotonation next to

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• -cyanoethyl N,N-diisopropylchlorophosphoramidite (CEP-Cl) and DIPEA provides β-4Ac-Man-CEP when the reaction is performed at a temperature below −15 °C (15–30 min reaction time). When the reaction is carried out at room temperature, epimerization leads to 2,3,4,6-tetra-O-acetyl-α-ᴅ-mannopyranose (not shown

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• reductase, Nit: nitrilase, A: adenylation, C: condensation, E: epimerization, TP: transport. Comparison of the fcl BGCs in Xenorhabdus and Photorhabdus strains responsible for the fabclavine biosynthesis. a: X. szentirmaii, b: X. budapestensis, c: X. cabanillasii, d: X. indica, e: X. hominickii, f: X

• , A: adenylation, C: condensation, E: epimerization, TP: transport. Compound list of the fabclavine derivatives identified in this work. The structures are based on MALDI–HRMS and MALDI–MS2 analyses using the known structure of 1 as a reference [20]. The derivatives 1–4 and 17–22 were described

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• . Systematic kinetic studies using NMR experiments suggested that protonation of the intermediate 252 occurs from the sterically favored side, leading to the kinetically stable cis product (Scheme 42). Nonetheless, some epimerization under the reaction conditions took place leading to the thermodynamically

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• -benzyl-protected gluco and galacto derivatives [20][27][30][31]. In addition to exocyclic glycals mimicking putative planar transition states of substrates involved in enzymatic reactions, such as glycosyl transfer, mutase, and epimerization, endo-glycals are also of interest [21][22][32][33][34][35

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• -phenylethyl group]. As the closest analogues of Garner’s aldehyde (3a) and other chiral α-aminoaldehydes, e.g., 4, or aziridine aldehydes 6 do not undergo epimerization during preparation as well as in further transformations conducted in the presence of basic reagents because of the high barrier to inversion

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• relationship between the starting oxirane and the enyne product was always obtained, whatever the group transferred from boron to the oxirane carbon. These results revealed the stereospecificity of the reaction and suggested that no epimerization of the oxiranyllithium intermediate occurred. The present

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• bioinformatics as well as spectroscopy. First, we analyzed whether the isolated natural product possesses a D- or L-configured thiazoline ring. Previous studies had revealed that the D-thiazoline ring in pyochelin is due to an unusual methyltransferase-like epimerization domain in the biosynthesis protein PchE

• , fatty acyl-AMP ligase; ACP, acyl carrier protein; KS, β-ketoacyl synthase; AT, acyltransferase; KR, ketoreductase; C, condensation; A, adenylation; MT, methyltransferase; PCP, peptidyl carrier protein; TE, thioesterase. The asterisk indicates a methyltransferase-like epimerization domain. C) UV

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• , and, on the other hand, the ratio of diastereomers in the presence of the same catalyst strongly depends on the solvent used. This suggests that the dr is determined by the rates ratio of the catalytic reaction (which can occur with high or low diastereoselectivity) and the epimerization of products

• (8a:9a) reached 6.3:1, while the conversion is 82%. After 50 hours, the dr reached 3:1, while the reaction practically stopped. Further, we carried out a control experiment to evaluate the epimerization rate of product 8a in solution under the same conditions. For this purpose the individual

• diastereomer 8a was dissolved in chloroform-d and the formation of the second diastereomer 9a was monitored by 1H NMR. Surprisingly, we found that, along with the epimerization of (2R,3S)-8a to (2S,3S)-9a, retro-Michael reaction occurred (Figure 4). It is noteworthy that firstly the formation of sulfone 5a was

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• obtained as a diastereomeric mixture via an Ugi–Nenajdenko reaction using the 4-methyl-2,6,7-trioxabicyclo[2,2,2]octyl (OBO) ester 46 to avoid epimerization of the isocyanide, followed by a reductive amination and chromatographic separation of the isomers; a Passerini–Dömling IMCR led to the heterocyclic

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• tert-butyl ester 13a to the alcohol by portionwise addition of DIBAL and careful temperature control (slow warm-up from −78 to −30 °C) afforded the alcohol without α-epimerization, which was oxidized to aldehyde 15 (IBX, Scheme 3). Adamantyl ester 14 resisted reduction under the same conditions and was

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• , whereas the desired (+)-3-hydroxymethylartemisinin (2) was produced from 17 in two steps including epimerization and cleavage of the TES group in excellent yield (Scheme 3). Finally, we evaluated the antimalarial activity of (+)-3-hydroxymethylartemisinin (2) as well as of the derivatives 16 and 18

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• ] were not able to reproduce the deprotection of the benzoylated derivative 8b as described in the work of Mikhailopulo et al. [26]. Instead, they observed a substantial epimerization leading to a ca. 2:1 mixture of the β/α anomers of NR+Br− and recommended the use of 1,2,3,5-tetra-O-acetyl-β-D