Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• relative configuration of the major epimer of 8 (Figure 3) was established on the basis of a cross peak in the NOESY spectrum that correlated the methyl group at C3 with a methylene proton adjacent to the quaternary carbon of the side chain at C3a. The configuration at C3, adjacent to a carbonyl group, is

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• diastereoselectivity, which means that every single example has to be explored independently. The assignment of the configuration and preferred conformation of product 18 was conducted on the basis of NOESY NMR experiments. Our analysis was aided by the observation that the 2-epimer 19 was accessible by oxidation of

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• performed using “odorless” thioglycoside 155 and 149 as the donor and the acceptor [81]. Even with the combination of “disarmed” 155 and “armed” 149, the reaction gave rise to the desired disaccharide 157 in 87% yield. The same reaction of the corresponding 3-epimer 156 proceeded smoothly to give the

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• acetonitrile solvent system (isocratic) at 48% acetonitrile and 52% water for 1 hour with a flow rate of 20 mL/min and UV detection at 254 nm. Compound 1 (5.6 mg) eluted with a retention time of tR = 20.8 min and its epimer, 2 (2.8 mg) at tR = 22.3 min. Both peaks overlapped slightly at the centre giving 15.2

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• (dba)3 as catalysts, X-Phos as a ligand, Cs2CO3 as a base in toluene or DMF solvent under thermal heating or microwave irradiation [18]. We recently described halogenations [19] and Sonogashira couplings on ring A of 13α-estrone and its 3-methyl ether [20]. The 13-epimer of natural estrone is a non

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• ] (yield 90%) and subsequently reduced with metallic sodium in presence of imidazole and 1-propanol (yield 80%) yielding the 7β-OH epimer (UDCA) as imidazole salt. Notably, the regiospecific oxidoreduction of the 7α-OH group is achieved using weak oxidants: this behavior can be explained by the peculiar

• conformation of CDCA (the 7α-OH group is surrounded by alkyl chains, generating an hydrophobic environment that favors oxidation to the ketone, which is not the case for the other epimer). These data are supported by a density functional calculation or rather the differential change in electron density due to

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• . This constituted the key step of the first total synthesis of (30S)-apratoxin E and its (30R)-epimer. Comparing the spectroscopic data of these two diastereomers with those of natural apratoxin E unambiguously confirmed that (30R)-apratoxin E was the natural product and that (30S)-apratoxin E was

• actually 30-epiapratoxin E, thus correcting the originally proposed absolute configuration. Both diastereomers were tested for their antiproliferative activities in HCT116 cells, showing that natural (30R)-apratoxin E exhibited a higher activity than its (30S)-epimer. Due to their lower basicity, samarium

• under mild and neutral conditions. Among them, many syntheses of naturally occurring products have been described for the first time, such as those of the glucose-regulated protein 78 expression inhibitor agent prunustatin A, the antiproliferative agent apratoxin E and its C30 epimer, prebiscibactin

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

• Neha Rana,
• Manish Kumar,
• Vinod Khatri,
• Jyotirmoy Maity and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205

• ribo-trihydroxy sugar derivative starting from diacetone-D-glucose led to the formation of an inseparable 1:1 mixture of the required compound and its C-3 epimer, i.e., 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose [10]. Lipases have been used extensively for the selective manipulation of

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• direction there are some examples [37][69][76]. The hemiacetalization by itself does not guarantee the stabilization of an elemane. If compound 1 had to suffer a normal Cope (chair TS), it would generate the C5 epimer of 2 (2’, Figure 2). This epimer is 2.6 kcal/mol less stable than 1a, so the formation of

• 2’ from 1, as in case of 2, is thermodynamically forbidden. Epimer 2’ can also produce a hemiacetal (3’) but this compound has a higher energy than 3 by 4.2 kcal/mol; this is due to the C5 propenyl group in 3’ is axially oriented instead of equatorially as in 3. In contrast to 3, the formation of

• epimer 3’ from 1 is not thermodynamically highly favored. Therefore, the hemiacetal formation with the right orientation is fundamental to produce an elemanolide more stable than the (Z,E)-germacranolide. It has been proposed that the configuration of an elemane depends on the most stable conformation of

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• obtained in the absence of its epimer, epi-8. Moreover, the chemical entities described herein offer opportunities for studies in glycobiology, biomedicinal chemistry and drug design. The use of these compounds as starting material to access new small ligands as GPCR modulators is ongoing in our

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• residues or alternatively abstraction by an available water molecule. The resulting enol/enolate could tautomerize spontaneously back to the original substrate or its epimer, with only the epimerized substrate possessing the required C-2 methyl stereochemistry for subsequent reduction. This epimer would

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• of the naturally occurring indolizidine alkaloid (±)-tashiromine and its unnatural epimer (±)-epitashiromine are demonstrated through the use of enaminone chemistry. The impact of various electron-withdrawing substituents at the C-8 position of the indolizidine core on the preparation of the bicyclic

• [3] (Figure 1). To date this natural product and its unnatural epimer 2 have been the targets of numerous enantioselective and racemic syntheses [4][5][6][7][8][9]. Typical approaches to accessing the alkaloid’s indolizidine skeleton have included a key cyclisation onto the nitrogen atom of either a

• (±)-tashiromine (1) and its epimer (±)-epitashiromine (2) in an overall yield of 87% and in a 13:87 ratio, which matches the diastereoisomeric ratio in the precursor (Scheme 3). Pure samples for characterisation could be obtained by flash column chromatography on silica gel using a 95:4.75:0.25 mixture of

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• to orthogonally protected amino acids 46 and 47 (Scheme 7) [58]. Installation of the C-2 stereocentre again began with Garner’s aldehyde 48 and Wittig olefination, followed by Sharpless dihydroxylation to stereoselectively afford diol 49 [59][60]. The C-2 epimer was accessed via Still–Gennari

• cyclic guanidines 51 and 52 was initiated through cleavage of the N,O-acetonide and guanylation using isothiourea 33 activated with HgCl2 (Scheme 8). Cyclisation of the guanidine afforded protected β-hydroxyenduracididine 51 in 21% yield in seven steps from diol 49. The C-2 epimer 47 was converted to β

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• ]. Based on this approach, in 2009, Donohoe and co-workers also reported the first total synthesis of (+)-sylvaticin [92][96], the C12-epimer of cis-sylvaticin (40) using oxidative cyclization chemistry to establish both the 2,5-cis- and the 2,5-trans-substituted THF ring of the natural product. However

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• by conventional column chromatography and hence a detailed analysis of the stereochemical features of this transformation was possible. Configurationally homogeneous compound 4a furnished diastereomerically pure cyclization product 13a in excellent yield, whereas epimer 4b was converted into product

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• urea dipeptide 27 [96][97]. Starting from the uridine derivative 28 used in the synthesis of (+)-caprazol, Ichikawa and Matsuda built up muraymycin D2 and its epimer (Scheme 4). They used an Ugi four-component reaction with an isonitrile derivative 29 obtained from the uridine-derived core structure 28

• , aldehyde 30, amine 31 and the urea dipeptide building block 27. A two-step global deprotection then gave the desired muraymycin D2 and its epimer which could be separated by HPLC [96][97]. In 2012, Kurosu et al. also reported the synthesis of potential key intermediates for the total synthesis of

• muraymycin D2 33 (with an L-leucine unit) and its epimer (with a D-leucine unit) on the purified MraY enzyme from B. subtilis were determined. Both compounds showed good inhibitory activities with IC50 values of 0.01 μM and 0.09 μM, respectively. However, their antibacterial activities against several Gram

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• a case the reaction is unexpectedly sensitive to minor steric alterations of the substrate because the C-4 epimer 15 (Scheme 3) did not react. An internal fluorine attack from the β-face of the tetrahydropyran ring through a concerted (Scheme 4C) or contact ion-pair (Scheme 4D) SNi mechanism cannot

• to furnish acetylated 3-fluoro-GalNAc 6 isolated as a separable mixture of anomers. The D-galacto configuration of 6 is manifested by the lower 3JH3,H4 coupling value (3.4 Hz, α-anomer) in comparison with that of its C-4 epimer 5 (8.6 Hz, α-anomer). Acetolysis of the internal acetal in 26 proceeded

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• afforded lactone 64. For the introduction of the side chain, the enolate derived from lactone 64 was treated with 1-bromo-4-methylpent-2-ene, giving a 1:6 mixture of coraxeniolide A (10) and its epimer 65. By equilibration with triazabicyclodecene (TBD), the ratio of 10:65 could be inverted to 3:1. In

• reactive methylenetriphenylphosphorane was used. Finally, α-alkylation of the lactone with iodide 83 provided coraxeniolide A (10) and its epimer in a 1:6 ratio which could be reversed to 4:1 by base-mediated equilibration. Purification by column chromatography, allowed the two epimers to be separated and

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• (+)-β-hydroxyhernadulcin isomer (Figure 1), which has been described as a sweetener [39]. Intrigued by the behavior of 3a we prepared the epimer 3d ([α]D −107° (c 1.2, CHCl3) vs lit. [8] [α]D −118.4° (c 0.5, CHCl3)) by the acid catalyzed racemization of C(6) stereogenic center. Remarkably, the absolute

Cross-metathesis reaction of α- and β-vinyl C-glycosides with alkenes

• Ivan Šnajdr,
• Kamil Parkan,
• Filip Hessler and
• Martin Kotora

Beilstein J. Org. Chem. 2015, 11, 1392–1397, doi:10.3762/bjoc.11.150

• quantitatively the same mixture of epimeric 1-(D-galactopyranosyl)prop-2-enes that were dissolved in ethanol and treated with ether. This allowed the α-epimer to precipitate and it could afterwards be isolated as a pure crystalline product in 60% yield [42]. Its acetylation afforded 1-(tetra-O-acetyl-α-D

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• methylenedioxyphenyl groups at C-10 and C-11. The NOESY spectrum of 7b exhibited a NOESY correlation between H-8 and H-2′ showed the syn relationship between these two groups but no correlation between H-8 and H-10 was observed, suggesting 7b to be the C-10 epimer of 7a. A correlation of H-10 to the H-9b, which was on

• protons (Figure 5) [26]. Overall this represents an anti-relationship between H-8 and H-10 confirming 7b to be the C-10 epimer of 7a. The ratio of diastereoisomers in ketal 22 was 1:1, however in the cyclised products 7 the ratio of diastereoisomers 7a to 7b was 1.6:1. This suggests partial isomerisation

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• )-protected Z-17 in the presence of (S,S)-Me-DuPHOS-Rh thus furnished thymidine-derived nucleosyl amino acid (S)-19 in 94% yield, and its 6'-epimer (R)-19 was obtained from the same starting material in 99% yield using catalytic amounts of (R,R)-Me-DuPHOS-Rh (Table 1, entries 1 and 2). Both transformations

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• primary alcohol of the side chain was oxidized with Dess–Martin periodinane (DMP) to give aldehyde 183. The latter was subsequently reacted with trimethylsilyl ketene acetal 184 in the presence of oxazaborolidinone 185 to afford aldol product 186 and the C22-epimer as only isomers in a 1:1 mixture. Dess