Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• position 2 underwent ca. 6% epimerization to yield 7 as a mixture of 4 stereoisomers. The synthesis of 2,6,8,12-tetramethyltrideca-2,4-diene (8) was completed by Wittig reaction using (3-methylbut-2-en-1-yl)triphenylphosphonium bromide [15]. As expected, the obtained mixture of all possible stereoisomers

• , followed by oxidation, yielded the aldehyde 10, which was chain elongated by Wittig reaction with [(2E)-1-methylbut-2-en-1-yl]triphenylphosphonium bromide [17] to afford the protected dienol 11 as a mixture of 4 racemates. This was due to partial epimerization at position 2 of the aldehyde 10 and the less

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• was still active, because it had been shown in several SAR studies that limited variation of the amine or alcohol component at the C-terminal amide or ester moieties of the dolastatin family members can be tolerated without much loss of cytotoxicity. This includes epimerization of the thiazole

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• isomerization to the desired cis-isomer 9 at elevated temperature (≈200 °C [1][2], lowered for more conjugated systems). The isomerization pathways have been suggested to proceed either via the formation of intermediate diradical-species (pathway A, Scheme 3) [16][20][26][27] or through one-center epimerization

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• affinity for opioid receptors [1]. In particular, most modifications of the furan ring tested to date dramatically reduce affinity for κ-OR [1], although small substituents at C-16 have little effect (Figure 1). Unexpectedly, epimerization at C-12, inverting the configuration of the furan ring, reduces

• chromatography, blocking the column. This was therefore extracted from the crude product with hot water. Our results conflict with a previous report that heating 1 in acetic acid led to deacetylation and epimerization [29]. In our hands, 1 was freely soluble in glacial acetic acid and was recovered unchanged

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• deleterious epimerization of the existing stereocenter in Garner’s aldehyde. Keywords: asymmetric synthesis; Garner’s aldehyde; natural product synthesis; L-serine; Introduction “The universe is a dissymmetrical whole. I am inclined to think that life, as manifested to us, must be a function of the

• -toluenesulfonic acid and 2,2-dimethoxypropane (DMP) in refluxing benzene (Scheme 1) [24][25]. Reduction of the methyl ester 4 to aldehyde 1 was performed with DIBAL-H (175 mol %) at −78 °C. Garner later reported that they had detected some epimerization of the chiral center (5–7% loss of ee down to 93–95% ee) [26

• (Hünig’s base, DIPEA) inhibits the epimerization (Scheme 3) [28]. With DIPEA as the base they could isolate the aldehyde (S)-1 with an enantiopurity of 96–98% ee. The drawback of this route is an additional reaction step, the “overreduction” of the ester 4 to alcohol 6 and the necessary re-oxidation to

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• indicates that a (partial) epimerization at C-4 occurs under the reaction conditions employed. The diastereoselective reduction of the carbonyl group with L-selectride afforded the α-azidotetrahydrofuranones 9 and 10 in 66% yield over three steps. Subsequent hydrogenolysis of 9 and 10 afforded a mixture of

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• quantitative recovery of unreacted starting material, the 6-MOM-protected precursor 29 underwent cyclization to the protected decanolide 38 [31] in 67% yield. Deprotection of 38 was accomplished with TFA in dichloromethane at ambient temperature without noticeable epimerization or elimination of water

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• rare sugar [25]. More interestingly, D-psicose has also been used to prepare several D-psicose containing disaccharides, aiming to learn the function of the rare sugar containing oligosaccharides and glycosides [27]. D-Psicose can be prepared through the epimerization of D-fructose at C-3 catalyzed by

• respectively. As these two enzymes showed high preference towards D-psicose, they were both renamed as DPEase as well. The activity of these two enzymes is strictly metal-dependent and requires Mn2+ as the optimum cofactor. Under optimal conditions, the epimerization yields were 32% and 28%, respectively [35

• galactitol catalyzed by Pseudomonas sp. ST 24 and the production yield was as high as 70%. The possible transformation route from galactitol to D-sorbose in this strain was deduced as follows (Scheme 4): the substrate galactitol is dehydrogenated at C-2 to afford D-tagatose followed by C-3 epimerization [43

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

• Peter A. Wade,
• Alma Pipic,
• Matthias Zeller and
• Panagiota Tsetsakos

Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251

• . Epimerization occurred at C-6 (the C-atom attached to the nitronate O-atom). An intermediate cyclic zwitterion would seem to be present and is consistent with observed relative rates of isomerization. The rate (and success) of the thermal [3,3]-sigmatropic rearrangement of O-allyl nitronic esters appears to

Non-cross-linked polystyrene-supported 2-imidazolidinone chiral auxiliary: synthesis and application in asymmetric alkylation reactions

• Quynh Pham Bao Nguyen and
• Taek Hyeon Kim

Beilstein J. Org. Chem. 2013, 9, 2113–2119, doi:10.3762/bjoc.9.248

• ]. Additionally, in the solid phase asymmetric alkylation reactions, in which Evans' 2-oxazolidinone chiral auxiliaries were used, the yield and stereoselectivity were too dependent on the base, reaction time, and supported resins. As an example, the base-catalyzed epimerization of the chiral center was

• responsible for epimerization was removed before adding the alkylated reagents [17], to obtain the high stereoselectivity control, the NCPS-supported 2-imidazolidinone chiral auxiliary 3 was simply prepared and asymmetric alkylations of it proceeded smoothly to produce the products in excellent

• acids 8a, 8b, and 8c in excellent ee values (Table 4, entries 1–3). To our surprise, although the asymmetric methylation proceeded very well with excellent diastereocontrol (>99 de), epimerization occurred under NaOH cleavage condition. Consequently, chiral acid 8d was obtained in only 89% ee (Table 4

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