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

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• reaction that leads to the final cis-product 21. The thermodynamically favorable trans-product 21 can be obtained through a tetramethylguanidine (TMG)-catalyzed epimerization process. Other possible electrophiles have been contemplated in the Friedel–Crafts alkylation of indoles. For instance, Jørgensen’s

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• epimerization to the sole product 193. Their postulation is based on the fact that Henry reactions are typically reversible, so 194 and 195 could be involved in a retro-Henry and subsequent diastereoselective Henry reaction, where the stereochemical outcome is inducted by the C2 stereochemistry. This is further

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• /epimerization can again be an issue in special cases [24]. However, the use of amines as chiral auxiliaries has been seldom exploited in peptidomimetic synthesis [16][25][26] because the need to remove the auxiliary reduces the number of diversity inputs and increases the number of synthetic steps. From the

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• additional modifying modules, e.g., epimerization domains, resulting in a greater structural variety than ribosomal peptides usually have. Two examples are the membrane disrupting decapeptide antibiotic tyrocidine A (14) [34] and teixobactin (15) [35], a recently discovered multi-target antibiotic rising

• promoter exchange [45] in the native host. Bioinformatics allowed for the annotation of several epimerization domains in the kollosin A NRPS, but it is hard to determine the actual activity of each of these functions. To overcome this problem, L-[2H8]valine, L-[2H10]leucin, L-[2H7,15N]tyrosine und L

• -[2H5,15N]threonine were fed to P. luminescens. The loss of one deuterium atom for an incorporated labeled amino acid (from Cα) directly supports an epimerase function within the corresponding NRPS module, and the incorporated building block can be assigned as D-configured. In this example, epimerization

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• each of E isomers goes through an oxocarbenium type transition state that have different stereochemistry on C-8. That reflects in formation of the two isomeric products 3 and 4, with the latter anomerically stabilized and thermodynamically more stable. In this case the complete epimerization to 8S

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• -aminocyclooctenecarboxylate (±)-3 underwent epimerization at C-1, leading after 18 h to an equilibrium mixture of cis and trans amino esters (1:1 ratio determined by 1H NMR on the crude mixture), the required trans isomer (±)-7 being separated from the cis counterpart and isolated in a yield of 48% by means of column

• chromatography on silica gel (n-hexane/EtOAc 1:4) to give the dihydroxylated amino ester. General procedure for epimerization of the cis-amino ester To a solution of cis N-protected amino ester ((±)-3 or (−)-3) (3.3 mmol) in EtOH (30 mL), EtONa (1.5 equivalents) was added at 0 °C and the mixture was stirred at

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• nucleosides and 2’-oxa-3’-aza-modified nucleotides. Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides. α–β Epimerization. Synthesis of triazolyl isoxazolidinyl-nucleosides 13 and 14. Reagents and conditions: a) Tosyl chloride, TEA, CH2Cl2, rt, 24 h; b) NaI, acetone, reflux, 72 h; c) NaN3, CH3CN/H2O (1:10) in the

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• barrier was found to be high as no epimerization was detected up to 150 °C, and consistent with this, density functional theory calculations give an inversion barrier of over 40 kcal/mol. Keywords: acylphosphine; acyl phosphite; chiral; DFT; NMR; nucleic acids; oligonucleotides; Introduction Antisense

• P-chiral phosphorothioates, a trivalent dinucleoside phosphorus moiety is required that undergoes rapid epimerization under the sulfurization conditions – that is, the goal was to carry out a dynamic kinetic resolution with formation of a single epimeric phosphorothioate. In order to carry out the

• required dynamic kinetic resolution, it was hypothesized that acylphosphonites 1 might undergo rapid epimerization by comparison to their known acylphosphine analogs 2 (Figure 1). Mislow previously showed that trialkyl and triarylphosphines slowly undergo epimerization only at temperatures above

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• equivalent with aldehydes the situation is more complicated. The reaction of (S)-10 with acetaldehyde under strongly basic conditions led to the (R)-threonine complex 29 (inverse configuration relative to that of the proline moiety of (S)-10 due to epimerization on C-2), but when a weaker base such as

• Figure 4 and Supporting Information File 1) [28]. However, the product ratio changed in time from 95:5 after 30 s through 70:18 after 10 min to 5:95 after 24 h at ambient temperature. This epimerization comes along with a possible rearrangement in the Ni complex. The newly formed hydroxide group of the

• conditions at low temperature and to quench the reaction after a short time to avoid epimerization of 28. This modified protocol indeed gave the (R)-allo-threonine (4) in relatively poor yield [7.5% for the Ni complex, 91% (7% overall) for the amino acid], but with high enantiomeric purity in two steps

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• yield was improved from 60 to 71% by decreasing the substrate concentration from 2.0 to 1.0 mM (Table 1, entry 4). During the MNBA-mediated lactonization, no epimerization occurred at the α position of lactone carbonyl group. Thus, the total synthesis of the proposed structure of 1 was achieved. We next

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• because of epimerization [12]. To circumvent this problem, we initially attempted to protect the ketone group prior to chemical conversion (Scheme 1). Compound 1 was acetylated (Supporting Information File 1) and subjected to protection as 1,3-dithiane [13] or 1,4-dinitrophenylhydrazone [14]; however

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• system), the catalytic effect of L-proline resulted in an increase in the reaction yield. Moreover, epimerization on the C-1 carbon atom of the starting aldehyde 88 was also suppressed. The latter effect was attributed to the preferential activation of methyl 3-aminocrotonate by L-proline via the

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• potent Oxyma-based uronium salt. Dependent on the bulkiness of the amino acids to be coupled and the chemical conditions such as its solubility and its stability, the decision of the proper coupling reagent, offering enhanced reactivity by simultaneous reduction of epimerization, is of high relevance

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

• Łukasz Górecki,
• Artur Mucha and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 883–889, doi:10.3762/bjoc.10.85

• solvent, instead of benzene, the reaction time was shortened to 7 hours while maintaining the same yield [35]. Epimerization, that occurred at the neighboring C8 atom, resulted in formation of two diastereomeric products: quininone 11 and quinidinone 12 in a 50:50 ratio. The mixture of ketones 11 and 12