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A procedure has been developed for the synthesis of a new chiral building block for epothilone analogs starting from L-malic acid.

A simple, convergent, and efficient approach for the total synthesis of the bioactive E- and Z-isomers of cytospolide-D is described. The key features of the synthetic strategy include stereoselective methylation, regioselective epoxide opening, olefin cr

A new synthetic route to N-Cbz-cis-(3R,4R)-3-methylamino-4- methylpiperidine, key intermediate for CP- 690,550, was disclosed with L-malic acid as the chiral pool starting material. The title compound was obtained in 16 steps with a total yield of 26% and

Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described. The pivotal C26-C40 DEF bis-spiroacetal was assembled by a double Sharpless asymmetric dihydroxylation/acetalisation cascade process on a linear diene intermediate, configuring the C31 and C35 acetal centres under suitably mild acidic conditions. A C1-C16 alkyne fragment was constructed by application of an oxy-Michael reaction to introduce the A-ring tetrahydropyran, a Sakurai allylation to install the C9 hydroxyl, and a 1,4-syn boron aldol/directed reduction sequence to establish the C11 and C13 stereocentres. Two different coupling strategies were investigated to elaborate the C26-C40 DEF fragment, involving either a C17-C25 sulfone or a C17-C24 vinyl iodide, each of which was prepared using an Evans glycolate aldol reaction. The remaining C43-C47 vinyl stannane fragment required for introduction of the unsaturated side chain was prepared from (R)-malic acid.

(Figure Presented) Wasp spider looking for a mate: Female wasp spiders (see picture) use trimethyl methylcitrate as a volatile cue to attract males. The experiments were performed on a sunny meadow, showing for the first time that spider traps can be used to trap spiders in the field (photo: Helen Sandford).

A productive total synthesis of both enantiomers of berkelic acid (1) is outlined that takes the structure revision of this bioactive fungal metabolite previously proposed by our group into account. The successful route relies on a fully optimized triple-deprotection/1,4-addition/spiroacetalization cascade reaction sequence, which delivers the tetracyclic core 32 of the target as a single isomer in excellent yield. The required cyclization precursor 31 is assembled from the polysubstituted benzaldehyde derivative 20 and methyl ketone 25 by an aldol condensation, in which the acetyl residue in 20 transforms from a passive protecting group into an active participant. Access to fragment 25 takes advantage of the Collum-Godenschwager variant of the ester enolate Claisen rearrangement, which clearly surpasses the classical Ireland-Claisen procedure in terms of diastereoselectivity. Although it is possible to elaborate 32 into the target without any additional manipulations of protecting groups, a short detour consisting in the conversion of the phenolic -OH into the corresponding TBS-ether is beneficial. It tempers the sensitivity of the compound toward oxidation and hence improves the efficiency and reliability of the final stages. Orthogonal ester groups for the benzoate and the aliphatic carboxylate terminus of the side chain secure an efficient liberation of free berkelic acid in the final step of the route. Queue up: Three deprotection and three bond-forming reactions, all of which are effected just by a trace of HCl, zip an easily attained enone to the polycyclic core of berkelic acid in diastereomerically pure form and essentially quantitative yield. This cascade process paves the way to a concise and effective total synthesis of this alleged metalloproteinase-3 inhibitor and cytotoxic metabolite derived from an extremophilic fungus.

A stereoselective synthesis of the pentaketide lactone (3R,4S,5S,9S)-3,5,9-trihydroxy-4-methylundecanoic acid δ-lactone has been achieved.

The intramolecular protective group (benzylidene acetal) assisted syn-1,3-diol synthesis has been efficiently utilized in a short synthesis of 6-epiprelactone-V starting from (S)-malic acid.

Diastereoselective methylation of dimethyl (S)-malate (8) followed by two three-step reductive dehydroxylation procedures afforded dimethyl (R)-2-methylsuccinate (16) in 80.2% and 84.7% ee respectively, the later was further transformed into the natural enantiomers of ant venom alkaloids (R)-leptothoracine (1) and (R)-3-methyl-N-(2-phenylethyl)pyrrolidine (2) and (3R, 2'S)-3-methyl-N-(2-methylbutyl)pyrrolidine (3).

The aldol reactions of ketene silyl acetals with reactive aldehydes proceed smoothly in water to afford the corresponding aldol products in good yields. (C) 2000 Elsevier Science Ltd.

Degradation of the novel polyketide herbicide herboxidiene leads to useful fragments for further analogue synthesis and also enabled determination of the absolute configuration of the natural product via asymmetric synthesis of the respective fragments.

A method for the preparation of diphosphineruthenium complexes from a range of diphosphine precursors is described.The stable products, of general formula P2Ru(allyl)acac (P = phosphine ligand), do not catalyse the hydrogenation of alkenes but can easily be converted into catalytically active species by reaction with trimethylsilyl trifluoromethanesulfonate.The chemistry involved in this transformation is discussed.Catalysis of the hydrogenation of a range of alkenes, and direct comparison with related rhodium reductions, is described.Some mechanistic insights are gained through additions of D2 to alkenes and parallel hydrogenations on deuterated solvent, supporting the intervention of conventional dihydride and alkyl hydride intermediates which undergo exchange with solvent at both stages.

Construction of the trisubstituted double bond of the C11-C28 subunit of avermectin A1a and B1a has been achieved in a five-step sequence.

Reduction of ethyl 3-methyl-2-oxobutane-1,4-dioate (3) with sodium borohydride furnishes a 6:1 mixture of ethyl erythro-2-hydroxy-3-methylbutane-1,4-dioate (8) and ethyl threo-2-hydroxy-3-methylbutane-1,4-dioate (18).Hydrolysis of this mixture with aq. hydrochloric acid gives a mixture of acids from which pure erythro-2-hydroxy-3-methylbutane-1,4-dioic acid (4) has been isolated.The stereochemistry of 4 has been establishrd by PMR and by transforming it to the anhydride, erythro-dihydro-3-acetyloxy-4-methyl-2,5-furandione (26).

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In order to synthesize four optically active methyl 2-methylmalates (10-13), microbiological asymmetric reduction of the corresponding dimethyl 2-methyl-3-oxosuccinate (9) was carried out.The β-keto diester 9 was found to be reduced by fermenting baker's yeast (Saccharomyces cerevisiae) and Candida albicans to afford a mixture of the (2R,3R)-isomer 10 and the (2S,3R)-isomer 11.Although the optical purity of 10 produced by Candida albicans was reasonably high (95percent e.e.), optical yields of other products were unexpectedly low.However, identification of the four possible isomers 14-17 was found to be easily carried out by means of nuclear magnetic resonance spectroscopy.Keywords - α-methyl-β-keto ester; methylmalate; asymmetric reduction; microbiological reduction; yeast; methyl 2-methylmalate

(+)-Pantolactone (13) has been synthesized from (-)-(S)-dimethyl malate (7) in 40percent yield in a short sequence involving double alkylation (7 -> 10 -> 11), selective hydrolysis (11 -> 12) and subsequent reduction (12 -> 13).Through variation of the alkylating agents and preparation of the two diastereomeric 3-ethyl-3-methyl malates 14 and 15 it was possible to show that the diastereoselectivity of the second alkylation step is brought about by preferential attack from the Re-face of the critical enolate (9, see also Scheme 1).This knowledge, in turn, has been exploited for the synthesis of a sample of pantolactone specifically enriched with 13C in its Si-methyl group.Analysis of the 13C-NMR. spectrum of this sample together with the results of biosynthetic experiments previously reported by Aberhart demonstrates that the biological hydroxymethylation of 2-oxoisovaleric acid (3) to 2-oxopantoic acid (4), an important step in the biosynthesis of pantothenic acid, takes place in a retention mode (cf.Scheme 2).

The absolute stereochemistry of serricornin (4,6-dimethyl-7-hydroxy-3-nonanone) was established as 4S, 6S, 7S by synthesizing both (4S, 6S, 7S)-isomer and its antipode.Only the natural enantiomer was bioactive.by

The absolute configuration at C-6 and C-7 of serricornin was established as (6S, 7S) by synthesizing its (6R, 7S)-erythro and (6R, 7R)-threo isomers.

As a contribution to the much discussed diastereoselective synthesis of enantiomers of open chain compounds, >90percent erythro-selective branching of malic esters by alkylation of the doubly deprotonated derivative 2 (alkoxy-enolate) with methyl, allyl, and benzyl halides in THF at -78 deg (- 3aa, 3ba, 3bb, 3bc, Table 1) is described.A second alkylation (- 4) and addition of 2 to acetone (- 5) are also possible.Cyclization of 2 to the enantiomerically pure trans-epoxides 6 is achieved by treatment with iodine.Cuprate opening of 6b furnishes the same product 3ba obtained from the methylation of 2b, establishing the configurational assignment.