Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• state becomes unlikely and then the selectivity is important. Our model is in agreement with the diasteroisomeric ratio results. In fact, a total diastereoselectivity was observed, including 5d (R = Ph) since an epimerization of the initial asymmetric center was observed, therefore racemic trans-isomers

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

• McMurry coupling to the diol, followed by two-step epimerization at C2. Assembly of the envisaged cyclization precursor 27. Structure analysis of diastereomeric cyanohydrins 29 and 30. Formation of allenes 32 and 34 from sterically crowded propargylic alcohol 31. Supporting Information Supporting

Heterogeneous acidic catalysts for the tetrahydropyranylation of alcohols and phenols in green ethereal solvents

• Ugo Azzena,
• Massimo Carraro,
• Gloria Modugno,
• Luisa Pisano and
• Luigi Urtis

Beilstein J. Org. Chem. 2018, 14, 1655–1659, doi:10.3762/bjoc.14.141

• -isopropyl-5-methylcyclohexanol ((−)-menthol, 1i). The reaction afforded an almost 1:1 mixture of only two diastereoisomers as determined by 1H and 13C NMR analysis of the crude reaction mixture, thus suggesting that it occurs with no epimerization at C1. This result was confirmed by submitting compound 3i

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

• lanyamycin epimers 1 and 2 mainly were observed in the side chains of the 16 membered macrolactone. As consequence of the epimerization, the conformation of the amide part of the side chain was adjusted. Particularly, the methyl group C-43 next to the epimeric centre was shifted from 0.87 ppm to higher field

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• to Vasellas' procedure [31][32] – with benzylamine under the reductive amination conditions afforded an inseparable mixture of two products differing in the configuration at the C2 center (12a and 12b; Scheme 2); such a phenomenon – epimerization under these conditions – is known [33]. The

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

• several research groups to focus their attention on the development of biotransformations with non-pathogenic, easy-to-manage microorganisms, and their enzymes. In particular, the enzymatic reactions involved are selective hydrolysis, epimerization of the hydroxy functions (by oxidation and subsequent

• in this review. C12 Dehydroxylation Chemical dehydroxylation UDCA can be obtained by a multistep chemical synthesis starting from CA. Two main steps are involved: the dehydroxylation at C12 and the epimerization of the 7-OH group. In order to achieve chemical dehydroxylation, firstly CA has to be

• ]. Biocatalytic C12 dehydroxylation In contrast to the reports on the epimerization of CA and CDCA with enzymes (see below ”Enzymes for the production of UDCA from CDCA”), the dehydroxylation of CA remains an undiscovered field for microbiologists and biochemists. To our knowledge, the only evidence of a

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• material to confirm that the process did not induce any epimerization. This methodology was then extended to the synthesis Gly-ψ[(E)-CF=CH]-Gly (not shown). Finally, Dory and co-workers reported the synthesis of Fmoc-Gly-ψ[(Z)-CF=CH]-Phe (Scheme 9) [36].Their work was inspired by the methodology reported

• -Ser-Phe-Arg-Phe-NH2 and Gly-ψ[(E)-CF=CH]-Gly-Phe-Ser-Phe-Arg-Phe-NH2 (see Scheme 7), representing the seven last amino acids of the neuropeptide 26Fra [34]. For the analogue containing the Gly-ψ[(Z)-CF=CH]-Phe isostere, epimerization was observed during last stages of the synthesis. The two

• isomerization or epimerization, cyclic pseudopeptides using Fmoc SPPS [48][50]. Biological studies were conducted on monofluoroalkene-containing analogues of FC131, which is a known antagonist of the chemokine receptor CXCR4. The latter has implications in cancer metastasis and HIV 1 infection. Anti-HIV 1

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• 1 and 2 were obtained by epimerization at C9. Mixtures of the isomers of 1 were formed in TBAF desilylation of Cinchona 4-TMS-triazole derivatives. Partial isomerisation of 2a into 2b was performed by transient deprotonation using in situ generated sodium methylsulfinylmethylide (Scheme 1). Both

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• partial epimerization of the residue. Finally, ester 4 was prepared by treatment of 6 with 3 equivalents of the 2,2-difluorodiazoethane (Scheme 1C). The reaction was performed smoothly using chloroform as a solvent giving a good yield (94%). We also attempted to perform the reaction in an acetonitrile

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• amino acid analogues [22][23]. However, epimerization in the α-position frequently occurs under the alkaline reaction conditions of the Seyferth–Gilbert and the Corey–Fuchs reaction. In order to access propargylamines with modified side chains, we chose a de novo synthesis strategy, using Ellman’s

• ], it provides a versatile protective group for the amine during the conversion of the alkyne. Additionally, it’s chirality indicates epimerization and, for example in the Pauson–Khand reaction [14], allows the determination of the stereoselectivity of asymmetric conversions by simple 1H NMR experiments

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• the epimerization of the hydroxy group at C-2/C-3 is the inactivation process contributing to a constant level of the active phytohormone. 2β,3β-Diols 6 are available through Woodward–Prévost cis-dihydroxylation of Δ2-steroids 3 [21]. The diaxial diols 7 can be easily synthesized by an acid-catalyzed

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• next deoxyfluorination reaction (Scheme 4). Gratifyingly, the p-nitro group of 39a was found to completely shut down the neighbouring group participation pathway; the desired trifluoroalkane 40a was obtained in good yield with no evidence of rearrangement or epimerization. It was also possible to

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• the presence of EDC (coupling agent), a base and a small amount [29] of EtOAc as liquid grinding assistant. The role of oxyma was mainly to suppress amino acid epimerization during the coupling, a limited problem in the case of proline. Consequently, our first experiments did not involve this reagent

• it would avoid a potential pressure build-up (release of CO2) which could occur with NaHCO3. Noteworthy, no epimerization could be detected by NMR or HPLC analyses. Both peptides 7 and 8 were then deprotected and cyclized into the corresponding diketopiperazine 9. Palladium-catalyzed hydrogenolysis

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• 4 under conditions used by us before, i.e., by treatment with isopropylmagnesium chloride, gave a mixture of diastereomers 7a and 7b. It was probably due to epimerization on carbon C2 of the carbanion, formed after attack of the Grignard reagent on sulfur. To our satisfaction, utilization of the

• desulfinylation process leading to ester 11 [24]. Unfortunately in this case the stereogenic center at the carbon undergoes epimerization under these reaction conditions and 11 is obtained in racemic form. To study the scope and limitation of the silane reactivity and its selectivity we checked the influence of

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• ). Unfortunately, we observed two signal sets in NMR spectra (intensity 3:1) for the product which could not be attributed to conformers or rotamers as evidenced by variable temperature and NOESY NMR experiments. These results, and the fact that Cochrane also reported problems due to epimerization during

• macrolactonization suggested that a partial loss of stereochemical integrity had taken place during either cyclization or esterification [11]. The site of epimerization could not be determined with certainty, but most likely, the D-Ala residue was affected. As the assumed diastereomers could not be observed or

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• side-hydrolysis of sensitive functions, as well as epimerization of stereocenters [25]. The first condensation step leading to the thiazoline intermediate was successfully achieved, although in the presence of molecular sieves without KHCO3. The latter was then immediately dehydrated at low temperature

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• glycerol obtained after hydrolysis of the oil and washing with organic solvents must be evaporated with care, maintaining an acidic pH to minimize epimerization to 4α-phorbol [19]. Next, the recovery of phorbol from the resulting ca 10% solution of phorboids in glycerol is difficult under both normal- and

• was accompanied by partial epimerization to 4α-phorbol (2a) and erosion of the overall final yield. To streamline the recovery of phorbol in the deacylation step, croton oil was treated with sodium methylate. By replacing hydrolysis with transesterification, it was possible to remove fats from the

• detoxified reaction mixture by extraction with petroleum ether, making dilution with water unnecessary. Provided that the pH of the reaction did not exceeded 13, retro-aldol epimerization was also negligible, and undetectable by TLC control. Evaporation of methanol was straightforward and gave a solution of

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• of the later, many sources of structural micro-heterogeneities occur as the epimerization at the C-5 position of uronic acids, and N- and O-sulfation. Of paramount interest is the elucidation of the role of GAGs in their interactions with such important proteins as extracellular matrix proteins

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

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

• investigated under more controlled conditions in vitro. Critically, the researchers were able to generate exclusively 14C-(2S)- or (2R)-methylmalonyl-CoA (7 and 8, respectively) by enzymatically removing the enantiomeric substrate under conditions designed to minimize spontaneous epimerization. Using the

• . Indeed, selection of the (2S)-isomer, and correspondingly, the (2R) isomer of aminomalonyl-ACP, would simplify the biosynthetic mechanism in a number of polyketide pathways, as subsequent epimerization of the resulting pendant centers (vide infra) would not be required. Ketosynthases The next step in the

• additional epimerization step must occur in module 1 to yield the L-methyl stereochemistry present at C-4 (thus explaining the loss of deuterium from the 2-position when (2RS)-[2-2H]methylmalonyl-CoA was used, and its incorporation from solvent in the presence of unlabeled extender) (mechanism III, Figure 9

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• desired (+)-trans-6 isomer contaminated with very small amounts (4%) of the cis-isomer. Under the same reduction/epimerization conditions, (+)-(S)-5 was successfully transformed into (−)-trans-6 containing 7% of the corresponding cis isomer. Alkaline hydrolysis of both enantiomeric methyl esters (+)-6 and

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• materials 1 is expected to afford intermediates 3. Although 3 may be formed as a mixture of diastereomers because of the epimerization of the initial adduct, as described in a literature precedent on a similar reaction [24], this is of no consequence for the outcome of the reaction. The next step would

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

• in Schemes 4–6. Surprisingly, the presence of excess of the base triethylamine and the fairly long reaction times do not lead to noticeable epimerization of the precursor γ-ketoesters that would lead to an erosion of the observed stereoselectivity. In all examples the methoxycarbonyl group and the

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• developed organocatalytic conjugate addition–enantioselective protonations of α,β-unsaturated imides using thiols. Thiols are attractive nucleophiles due to their acidity, which facilitates deprotonation by amine bases and also reduces undesired competitive deprotonation and epimerization of the enolizable

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• for either coordination mode, which leads to poorer enantioselectivities in THF (Table 8, entry 6). We propose that acetone, being more Lewis basic than THF, has the effect of epimerizing the chiral-at-ruthenium intermediates formed prior to [2 + 2] cycloaddition. The rate of epimerization is much

• coordination. The pendant olefin prefers to approach the carbene anti to the aforementioned sulfoxide, resulting in the observed enantiomer of 53. In THF, the rate of epimerization is significantly slower than the [2 + 2] cycloaddition, which means that the enantiomeric ratios observed in the products are

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

• gave fluorhydrin 20 which was subjected to epimerization at C-4 by Latrell–Dax inversion to furnish 2-azido-3-fluoro compound 21 with the desired D-galacto configuration (Scheme 3). The geminal fluorine–carbon coupling value 2JC4,F = 17.7 Hz in 21 is characteristic for a gauche relationship between the