The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• for this system. The stereochemical outcome could be attributed to the sterically less demanding transition state 82b. The epimerization of 83 to 85 proceeded via an intermediate lactone and extended the route by seven steps. After having secured the cis-epimer 85, the diene moiety was introduced in

• sequence. The asymmetric intramolecular Diels–Alder reaction was then catalyzed by Kristensens’ catalyst (201) to give 202. A base-promoted epimerization of the aldehyde and a Horner–Wadsworth–Emmons reaction furnished 203, the most advanced intermediate reported so far. Just recently, the group of

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• reaction. The diastereoselectivities were greatly improved by prolonging the reaction time, which would allow for epimerization leading to the thermodynamically more stable products. The starting materials, 1,2-diamines 70, were readily prepared from natural amino acids in enantiomerically pure form. Xiao

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• ; then hydrazine monohydrate) [38][39][62]. Unfortunately, fluoride-mediated desilylation of allene 6c caused complete epimerization of the allenic chirality axis. Therefore, the silylallene was not used in further studies. The results of the gold-catalyzed cycloisomerization of the allenes 7 and 8 to

• epimerization of the allene, so that dihydrofuran 9b was isolated as a 4:1-mixture of diastereomers. As expected, the cycloisomerization of allenes 8 bearing an unprotected amino group is much slower [38][39] and requires rather forcing conditions. For a complete conversion of α-aminoallene 8a, 10 mol % of AuCl

• compound 2’-epi-11b in 4% yield, indicating a minimal epimerization of bromoallene 8b during the gold-catalyzed cyclization. The synthesis of azafuranomycin analogs was continued with the twofold Cbz-protected heterocycle 11a which was obtained with 79% yield by treatment of 10a with CbzCl and DMAP [63

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• 2-hydroxy compound 31 as a single diastereoisomer (as determined by 1H NMR) in 71% yield. Esterification with MeOMgCl [69] (which has been shown not to cause epimerization at the α-position [67]) and saponification [70] afforded (S)-2-hydroxy-15-methylpalmitic acid (32). The ketone 33 was isolated

The preparation of several 1,2,3,4,5-functionalized cyclopentane derivatives

• André S. Kelch,
• Peter G. Jones,
• Ina Dix and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 1705–1712, doi:10.3762/bjoc.9.195

• studies, or whether epimerization took place during the attempted conversion of the pentaalcohol to the pentabromide 17. The complete, structure-confirming spectroscopic and analytical data of 19 can be found in Supporting Information File 1. In closing this section on the preparation of bromine

Preparation of optically active bicyclodihydrosiloles by a radical cascade reaction

• Koichiro Miyazaki,
• Yu Yamane,
• Ryuichiro Yo,
• Hidemitsu Uno and
• Akio Kamimura

Beilstein J. Org. Chem. 2013, 9, 1326–1332, doi:10.3762/bjoc.9.149

• enhanced the yield of 2a to 58% (Table 1, entry 3). The enantiomeric excess of trans-2a was estimated to be 95% by HPLC analysis, which was the same ee level of precursor 1a. Thus, no epimerization at the C3 chiral center occurred during the reaction. The stereoselectivity was improved to 8:2. The

• analyses using ChiralPak ID and IC (Table 2, entries 1, 2, and 4), the enantiomeric excesses of most of products 2 were high, and their original values were maintained (Table 2, entries 3, 5, 6, 8, and 9). Interestingly, significant epimerization occurred during the reaction of 1h; the enantiomeric excess

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• triggered by exposure of trimesylate 2 or a related electrophile to ammonia. A sequential alkylation process would serve as a viable alternative in the event of problems with this approach. In turn, cis-fused trimesylate 2 could be derived from trans-fused tricyclic ketone 3 by epimerization and standard

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• undergo α-epimerization, oxidation had to proceed under mild conditions in order to avoid the formation of the undesired D-talosamine building block D-9 (Scheme 4). Several oxidation methods were tested (Table 2). All the reactions were performed sequentially without column-chromatographic purification of

• - and L-fucosamine building blocks. (A) Synthesis of aldehydes 6a and 6b. (B) Alkyne reduction by hydrosilylation–protodesilylation sequence (see Table 1). Synthesis of D-fucosamine building blocks 8a and 8b. Epimerization of aldehyde 6a. Synthesis of L-fucosamine building block L-8a from D-Garner

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• concept to avoid the epimerization of reactive intermediates, which has allowed them to carry out the enantioselective version of the above procedure. Thus, the use of a flow microreactor system has allowed the enantioselective carbolithiation of conjugated enynes, followed by the reaction with

• electrophiles to give enantioenriched chiral allenes. By high-resolution control of the residence time, the epimerization of a configurationally unstable chiral organolithium intermediate 23 could be suppressed. Using this method, n-butyllithium reacts with enynes 22 in the presence of chiral ligands, and the

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• of the THBC-DKP scaffold also in solution, compound 6 was converted into the N-methyl carboxyamide derivative 1a, by a two-step procedure (0.5 M LiOH, 0 °C, then MeNH2, TBTU, DIPEA), which was carefully conducted in order to avoid the easy epimerization of the C3 and C12a stereocenters. Spin-system

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• , aldehydes and amines [12]. The method involved a three-step stepwise sequence involving an organocatalyzed Michael addition, a reductive amination/intramolecular lactamization, and an epimerization step (Scheme 1). It culminated in the preparation of a 43-member library. Although this method permitted

• produced 3{1,1} in high yields and with high enantioselectivity, albeit with low diastereoselectivity. Such a low diastereoselectivity was of no concern in the originally reported procedure since the final potassium tert-butoxide promoted epimerization step produced a racemic mixture of a single

• diastereomer. In the case of an asymmetric synthesis, however, the initial diasteromeric ratio would be reflected in the enantiomeric ratio of the final products when the downstream epimerization step is taken into account; this is illustrated for the limiting case of high facial selectivity with respect to

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• -F04a was synthesised by using a modified Yamaguchi macrolactonization approach. Alternative methods of macrolactonization (e.g., Corey–Nicolaou) resulted in significant epimerization of the C-terminal amino acid during the cyclization reaction. The D-stereochemistry of the alanine residue in the

• naturally occurring cyclic peptide may be required for the antifungal activity of this natural product. Keywords: antifungal; cyclic depsipeptide; epimerization; lipopeptide; macrolactonization; peptides; Introduction The LI-F or fusaricidin class of cyclic depsipeptides are produced by a number of

• cases (Table 1, entries 1–3), analysis of the crude product mixtures showed that mixtures of cyclic diastereoisomers were obtained, indicating that the C-terminal amino acid underwent epimerization during the macrolactonization reactions (see Supporting Information File 1 for full experimental details

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• in a complete epimerization at the CH-acidic C-4 position, exclusively yielding the thermodynamically more stable iridomyrmecin B. All reaction steps were also carried out starting from enantiomerically pure (S)-limonene affording trans-fused iridomyrmecins A' and B'. Relative configurations of

• iridomyrmecin C, whereas treatment with p-toluenesulfonic acid in benzene under reflux conditions led to complete epimerization at C-4 and afforded iridomyrmecin D. All reaction steps were also carried out starting from enantiomerically pure (S)-limonene (3') and afforded iridomyrmecins C' and D'. Relative

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• steric strain. Due to the CH-acidity at the α-position of the formyl group, epimerization of the all-trans product 24 under acidic or basic conditions could be expected. Lange et al. reported the catalytic hydrogenation of a structurally close analogue, (5R)-1-formyl-2-methyl-5-isopropylcyclopent-1-ene

• palladium on carbon (10%) to be the method of choice [30]. Using this approach, the all-trans aldehyde 24 was almost exclusively formed. The presence of ammonium formate in the reaction mixture probably leads to an “in-situ” epimerization at C2 from the kinetically formed all-cis to the thermodynamically

• phosphate buffer (pH 4.5) afforded the carboxylic acid 25 without epimerization at C1 [23][31]. Subsequent deprotection of the TBDMS ether with tetrabutylammonium fluoride (TBAF) yielded 17, and lactonization with N,N-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) in dichloromethane

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• Gly) residues spread across its sequence, which allows one to design suitable segments each with an achiral residue at its C-terminus, thus reducing dramatically the usually considerable risk of epimerization during the coupling reactions. For the best choice of the step involving treatment with the

Synthesis of highly functionalized β-aminocyclopentanecarboxylate stereoisomers by reductive ring opening reaction of isoxazolines

• Melinda Nonn,
• Loránd Kiss,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2012, 8, 100–106, doi:10.3762/bjoc.8.10

• formed, then separated and isolated. The cycloaddition of nitrile oxide to trans-ethyl 2-aminocyclopent-3-enecarboxylate under similar conditions proceeded selectively with the formation of 6. Epimerization of 2 and 4 afforded trans derivatives 3 and 5 [48][49]. Since isoxazoline-functionalized molecules

Photochemical and thermal intramolecular 1,3-dipolar cycloaddition reactions of new o-stilbene-methylene-3-sydnones and their synthesis

• Kristina Butković,
• Željko Marinić,
• Krešimir Molčanov,
• Biserka Kojić-Prodić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2011, 7, 1663–1670, doi:10.3762/bjoc.7.196

• photoproduct 12 from the trans configuration, although the formation of 12 via epimerization of 11 could not be eliminated. It is also evident that there are several competitive processes, which are summarized in Scheme 5. On irradiation of 3a (trans) or 3b (cis) parallel competitive processes are in operation

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

• exposure to 0.5 M HCl, epimerization of the isopropyl group at C-3 occurs in near quantitative yield, giving adduct 13 (Scheme 10). The electron-withdrawing effect of the carbonyl moiety must increase the acidity of the C-3 proton to such an extent that the acidic media simply epimerizes at this center to

• . Hydrolysis to amino acids. Hydrolysis of analogue 6j. Epimerization at C-3 of 6g. Formation of quaternary Schöllkopf adducts employing a range of electrophiles. Supporting Information Supporting Information File 285: Detailed experimental procedures and analytical data for compounds 6a–j, 7b–c, 8a, 8d, 8e

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• catalyzed the epimerization of 14 yielding the epimer N-acetylmannosamine (15), which consequently was condensed by the second enzyme aldolase with pyruvic acid (16) to form the product 17 (Scheme 6). By appropriately adjusting the reaction parameters, such as pH, temperature and substrate concentrations

High chemoselectivity in the phenol synthesis

• Matthias Rudolph,
• Melissa Q. McCreery,
• Wolfgang Frey and
• A. Stephen K. Hashmi

Beilstein J. Org. Chem. 2011, 7, 794–801, doi:10.3762/bjoc.7.90

• -catalyzed conversion of the pure isomers. From the NMR spectra taken during the conversion (Figure 4), it could be clearly seen that no epimerization of the propargylic position occurred. In addition to the selective transformation to the phenols 37a and 37b as the main reaction products, partial removal of

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• is sometimes incomplete. This may arise due to a competitive gold-promoted cyclopropyl ring opening/epimerization/ring closure, both in cis and trans-cyclopropyl settings, which competes with the cyclization event, thus eroding the overall transfer of stereochemical information. Conclusion From the

Photoinduced electron-transfer chemistry of the bielectrophoric N-phthaloyl derivatives of the amino acids tyrosine, histidine and tryptophan

• Axel G. Griesbeck,
• Jörg Neudörfl and
• Alan de Kiff

Beilstein J. Org. Chem. 2011, 7, 518–524, doi:10.3762/bjoc.7.60

• with the corresponding amino acids or by the Nefkens procedure [9]. The latter procedure yields enantiomerically pure products (by optical rotation), whereas the thermal method leads to partial epimerization. Photochemistry of the tyrosine and histidine derivatives 8 and 9 The colorless phthalimides

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans – an approach to carbohydrate mimetics

• Fabian Pfrengle and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 75, doi:10.3762/bjoc.6.75

• ). We presume that an initially formed nitrone 22 probably undergoes base induced epimerization to generate the thermodynamically more stable trans-substituted nitrone 21. As shown below, the nitrone moiety of 21 can be regarded as a masked hydroxylamine, however, it should also be very useful for

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides

• Ana Maria Castilla,
• M. Morgan Conn and
• Pablo Ballester

Beilstein J. Org. Chem. 2010, 6, No. 5, doi:10.3762/bjoc.6.5

• peptide-coupling reaction of the all-S linear tetrapeptide. As discussed above, one of the two diastereoisomers is probably the outcome of the epimerization reaction experienced by the stereogenic center in the α-position with respect to the carboxylic group undergoing activation. Likewise, the two minor

• peaks should correspond to cyclic diastereoisomers formed from macrocyclization and concomitant epimerization reactions experienced by the minor linear tetrapeptide S,S,S,R also incorporated into the starting material. Figure 4b depicts the HPLC chromatogram obtained from the analysis of the purified

• techniques. Initially, we used HBTU/NMM [25][33][34] for activation of the intramolecular peptide bond formation. We observed considerable epimerization at the stereogenic α-carbon. We assessed the coupling reaction using different coupling methods, HATU/NMM [35] and PyAOP/DIEA [36], and found that although