(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• activity, if not an improvement [1]. Often-used bioisosteres include the tetrazole group for a carboxylic acid [2][3][4][5] and fluorine atoms in place of hydrogens [6][7]. The inclusion of fluorine can alter the polarity of a molecule and can also be used to prevent epimerisation, as seen in

• . Isomerisation to the desired cis-[2]-ladderanes 150 was achieved through epimerisation of the ester functional group (Scheme 16B) [63]. Transformation of the phenyl group (of 150a) or alkene group (of 150b) into synthetically versatile acid 151 and protected alcohol 152 was achieved by standard chemical

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• (Table 2). As the racemate of 3a was obtained in a higher diastereomeric ratio (6.3:1) we applied kinetic and thermodynamic conditions for the epimerisation of it (Table 2, entries 1 and 2, respectively). Unfortunately, in both cases the diastereomeric ratio decreased and the amount of more stable syn

• depicted). Reaction conditions: 0.2 M solution of 1 equiv of 1, 2 equiv of 2, 0.1 equiv of catalyst D, chloroform, at room temperature; isolated yields after column chromatography; ee determined by chiral HPLC. Screening conditions for the reactiona. Epimerisation of 3a. Supporting Information Supporting

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• ,S-configuration found in several monoalkylated tartaric acid motif-containing natural products. Keywords: alkylation; cycloaddition; diazoester; epimerisation; tartaric acid; Introduction Since their isolation was reported in the early 1990s [1][2], the squalestatins/zaragozic acids (e.g

• stereoretentive alkylation, then direct access to the stereochemistry present in the majority of these natural products is not possible. Nevertheless, a couple of isolated examples in the Chinese chemical literature from the late 1980s indicated that subsequent base-induced epimerisation of monoalkylated (p

• -(benzyloxy)benzylated and prenylated) tartrate acetonides favours R,S stereochemistry, providing access to piscidic acid (42) [26] and the tartrate residue of isoharringtonine (43) [28]. We studied the previously reported epimerisation of prenylated tartrate 33f, on 0.5 mmol scale ([28] 5 mmol), using NaOMe

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• determined on the basis of HT NMR and thermal epimerisation experiments. The structure of most presented atropisomeric derivatives of 2,6-dimethylpyridine was confirmed by single-crystal X-ray analysis. Racemic chiral, differently substituted atropisomers were also examined by 1H NMR spectroscopy in the

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• mechanoenzymatic transformations of amino acid [102][103][104][105][106][107], cellulose [108] or model lignin [109] substrates. Implicit within these studies is the resilience of chiral centres within both substrate and catalyst towards epimerisation during ball milling. This was also explicitly demonstrated by

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• which has then been extended at the 3- and 6-positions of the branching mannose unit. Amongst the possible ways to synthesise this key disaccharide [51][52] two have been used predominantly for the synthesis of N-glycan oxazolines. The OH-2 epimerisation approach, which uses a gluco-configured donor for

• epimerisation. Amongst the many syntheses [53][54][55][56][57][58] of N-glycan oxazolines using this approach, the use of Lev protection on the donor, first developed by Boons [59], and then triflation and nucleophilic substitution by acetate aided by sonication, first developed by Fürstner [60][61], appear to

• be optimal. An example that employed these key steps was used to synthesise a truncated complex biantennary N-glycan oxazoline [62], as shown in Scheme 4. Following the gluco to manno epimerisation process, selective deprotection of OH-3 of the mannose unit was followed by glycosylation and extension

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• stereoisomers, (4R,5R,6S)-11a and (4S,5S,6S)-11b, would be accessible via the same route from (2Z,4S)-20, but this compound was not obtained in sufficient quantity for a practical approach towards 11a and 11b. Therefore, these two stereoisomers were obtained by epimerisation at the α-carbon (C-4) under mildly

• basic conditions (Scheme 6). Following this approach, the epimerisation of (4R,5S,6S)-11c yielded (4S,5S,6S)-11b, while epimerisation of (4S,5R,6S)-11d gave (4R,5R,6S)-11a. The epimerisation products were added to the synthetic mixture of all eight stereoisomers, showing by enantioselective GC analysis

• ) headspace extract from D. clavata, c) enantioselectively synthesised (4R,5S,6S)-11c (Scheme 5), d) enantioselectively synthesised (4S,5R,6S)-11d (Scheme 5), e) coinjection of a) and epimerisation products of (4R,5S,6S)-11c (Scheme 6), and f) coinjection of a) and epimerisation products of (4S,5R,6S)-11d

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• the aldehyde 32 with DIBALH. Finally, a Brown crotylation [77] set the two vicinal stereogenic centers of 6 with high stereoselectivity. In total this route enabled an efficient and reliable access to this key fragment. However, one drawback of this sequence was a tendency of epimerisation at C1

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• ), peptidyl carrier protein with phosphopantetheine linker (PCP; green), condensation (C; red), epimerisation (E; dark blue), P450-recruitment (X; blue) and thioesterase (TE; light grey) domain; the peptide is shown at its distinct stages of biosynthesis; the amino acid cyclisation steps are depicted with

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• , unfortunately, gave a poor isolated yield of 26% and also underwent some epimerisation (25, 53% ee determined by chiral HPLC, Scheme 2). Additionally, a small amount of the product (25) reacted further with phenylboronic acid through the phenol to give 26 in 3% isolated yield. In the case of L-leucine methyl

• ester an isolated yield of 60% was realised, but this substrate also underwent partial epimerisation (27, 71% ee determined by chiral HPLC, Scheme 2). Using N-heterocyclic substrates as the nucleophilic partner with a range of different phenylboronic acids generally gave good isolated yields (19, 20, 28

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

• a first key step of the synthesis led to a 1:1 mixture of the two epimers 36 and 37, and the undesired lactone 37 could be epimerised and converted into 36 by treatment with DBU [98]. Epimerisation and simultaneous lactone opening could be achieved in another key step using L-valine tert-butyl ester

• exact stereochemical course of epicapreomycidine formation in muraymycin biosynthesis is unclear though as the stereochemical configuration at C-3 of the intermediate 3-hydroxy-L-arginine (107) has not been identified yet. It cannot be ruled out that an epimerisation reaction might be involved in the

• biosynthesis of 108, in particular with respect to other epimerisation steps in bacterial biosynthetic pathways [122]. Consequently, synthetic routes towards both 3-epimers of 3-hydroxy-L-arginine have been developed which would also enable the preparation of isotopically labelled congeners for biosynthetic

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• Michael adducts into the benzoin product. The prolinol catalyst 60, on the other hand, mediates the epimerisation of the less reactive diastereomer. This synergy leads to the enrichment of the diastereomeric ratio of the final product 64 (Scheme 38) [55]. Enders developed a closely related iminium-cross

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• yields, referred to the starting compounds 3/3', are reported in Scheme 2. No epimerisation reactions occurred during the hydrolytic processes as demonstrated via 2D NMR experiments (COSY, HSQC). Discussion In the Diels–Alder reaction of vinylindoles 1 with methyl 2-acetamidoacrylate (2), among tested

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

• unfavourable steric interactions (Figure 7). Reaction mechanism Although uncommon, epimerisation at position 8-C was reported earlier [62] in structurally similar compounds when exposed to analogous reaction conditions. A plausible mechanism of the transformations as discussed is presented in Scheme 2. The

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• ring-opening of the syn-cyclic sulfates does not produce syn-dibenzoate, and that epimerisation is not competitive with ring-opening. This was further supported by chiral HPLC analyses of the dibenzoates, which also suggests that clean conversion occurs, without epimerisation. All four dibenzoates had

• the chiral 19F{1H} NMR method revealed that the ee was unchanged from the diol 28a, confirming epimerisation was not occurring during the subsequent reactions (aldehyde 38a was of particular concern). The synthesis of alkenes 39 is particularly significant, as at this stage the crotonic acid route

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• of diastereomers (Table 4, entry 7). The loss of diastereospecificity may be explained by the long reaction time: we assume that syn-carbolithiation is followed by a partial epimerisation of the intermediate organolithium during the 24 h before the reaction is quenched. Related vinylureas will

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• protection of the vicinal diol, accompanied by methyl ester formation. The methyl ester 14 was subsequently reduced with DIBAL-H to give the aldehyde 15. In order to avoid epimerisation, this aldehyde was not purified, but filtered through Celite only and then reacted with allyl-tri-n-butyltin to give the

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• successful but led to N-tosylated compound 31 in 24% yield. A partial epimerisation at the benzylic position and slow decomposition of precursor 28 could also be observed under the reaction conditions applied, and none of the desired pyrrolidine derivatives could be found in the crude product. Purification

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• thermodynamically stable product (Scheme 6, Path A). - The third is similar to the second, but the two direct nitro-Mannich products A and B with the observed configurations at the 6 position preferentially lactamise, and there is a postcyclisation epimerisation at the stereogenic carbon bearing the nitro group

• fundamental synthetic tool. Further development is ongoing in our laboratory and the results will be disclosed in due course. Biologically active natural products and drugs containing the piperidine ring. Cyclic imines employed in nitro-Mannich/lactamisation cascade. Thermodynamically driven epimerisation of

• diastereomer 2m isolated in 5% yield. Possible explanations for the observed high stereoselectivities in the nitro-Mannich/lactamisation cascade. Thermodynamically-driven epimerisation of 5-nitropiperidin-2-ones 2m and 2m’. One-pot three/four-component enantioselective Michael addition/nitro-Mannich

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• -(−)-sparteine deprotonation step. Secondly, since epimerisation of the organolithiums is also slow enough for different d.r.'s of a stananne to yield different d.r.'s of a product (Table 3, entries 1 and 3), we can be certain that the secondary benzyllithium centre is macroscopically stable on the timescale of

Single enantiomer synthesis of α-(trifluoromethyl)-β-lactam

• Václav Jurčík,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2011, 7, 759–766, doi:10.3762/bjoc.7.86

• -methylbenzyl-β-lactam 5a with a modest diastereoisomeric bias (~50% de) indicating some epimerisation of the α-trifluoromethyl stereogenic centre, to a thermodynamic product ratio. This was supported in an analytical reaction by the observation of deuterium exchange at this stereogenic centre after the

• in an enantiomerically pure form. There was no evidence that benzylic cleavage of the (S)-α-(p-methoxyphenyl)ethyl moiety with CAN resulted in epimerisation at the stereogenic centre of the β-lactam. Finally, it was necessary to determine the absolute configuration of the resultant β-lactam. To this

Application of the diastereoselective photodeconjugation of α,β-unsaturated esters to the synthesis of gymnastatin H

• Ludovic Raffier and
• Olivier Piva

Beilstein J. Org. Chem. 2011, 7, 151–155, doi:10.3762/bjoc.7.21

• product ([α]D25 = +42.3 (0.76, CHCl3)). Similar discordances have been already observed in the case of gymnastatin N and were shown to be a consequence of a partial epimerisation at the C-2’ carbon of the natural compound's amino ester subunit [15]. Conclusion In conclusion, we have achieved the total

Carbasugar analogues of galactofuranosides: α-O-linked derivatives

• Jens Frigell and
• Ian Cumpstey

Beilstein J. Org. Chem. 2010, 6, 1127–1131, doi:10.3762/bjoc.6.129

• could offer a route to α-configured galactofuranoside pseudodisaccharides via a subsequent epimerisation of the unprotected C2 alcohol, analogous to the α-manno to α-gluco epimerisation route developed by Ogawa in the six-membered ring series [17]. In this paper we report our results on the synthesis of

• corresponding α-compounds can be made by an indirect route: Opening of a β-talo configured epoxide followed by C2 epimerisation. The very good regioselectivity in the epoxide-opening reaction indicates that steric and/or electronic effects favouring attack at C1 over C2 are more important than other factors

Bis(oxazolines) based on glycopyranosides – steric, configurational and conformational influences on stereoselectivity

• Tobias Minuth and
• Mike M. K. Boysen

Beilstein J. Org. Chem. 2010, 6, No. 23, doi:10.3762/bjoc.6.23

• . Because of the strong impact of the pyranose position 3 in ligands 3a–f on the stereoselectivity, we became interested in elucidating the influence of the stereochemistry at this position by both 3-epimerisation and 3-defunctionalisation. Inversion of the configuration at position 3 to give an allo

• yield. To prepare an allo-configured precursor for ligand synthesis, we decided first to use a previously described epimerisation sequence for 7 featuring Swern oxidation and subsequent reduction with sodium borohydride [25]. In our hands this method led to an inseparable product mixture in the second

• derivatives of gluco-configured bis(oxazoline) ligands 2 and 3 with 3-epimerisation or 3-defunctionalisation in the pyranose scaffold. Application in stereoselective cyclopropanation as a model reaction highlighted the strong impact of modifications at the pyranose position 3 on the asymmetric induction

Diastereoselective functionalisation of benzo-annulated bicyclic sultams: Application for the synthesis of cis-2,4-diarylpyrrolidines

• Susan Kelleher,
• Pierre-Yves Quesne and
• Paul Evans

Beilstein J. Org. Chem. 2009, 5, No. 69, doi:10.3762/bjoc.5.69

• explanation for this mixture of products, based on the high levels of diastereoselectivity observed in the similar examples discussed herein, is that the initially formed product begins to undergo epimerisation in order to place the larger (CO2Me) substituent on the least hindered face. Consequently, the

• complete epimerisation of this material was investigated using NaOMe (1 M) based on a literature report [26]. Pleasingly, the hoped for process did indeed lead to the formation of one diastereomer of carboxylic acid 26, which was formed from the methyl ester on hydrolysis following work-up (see Figure 4

• and crystallographic data). Although the yields described during this sequence are low at this stage, the successful epimerisation observed demonstrates that this approach represents a stereo-complementary method to those described in Scheme 1 and Scheme 8. With the lithiation chemistry described