The total synthesis of (À)-epothilone A by a convergent route is reported. The synthesis of the required key intermediates has been improved with respect to stereoselectivity and availability. The access to ethyl ketone 2 has been significantly improved by employment of chiral acetate equivalents, which provided higher optical and chemical yields. Key intermediate 3 was obtained by oxazolidinone auxiliary techniques and stereoselectively coupled with 2 by an aldol reaction. After esterification with thiazole fragment 4, (À)-epothilone A was finally constructed by using ring-closing metathesis.

The vinylogous Mukaiyama aldol reaction (VMAR) allows efficient access to larger segments for complex natural product synthesis, primarily polyketides, through the construction of vicinal hydroxyl and methyl groups as well as di and tri-substituted double bonds in one single operation. In this review, we will highlight stereoselective protocols that have been used in natural product synthesis and cluster them into the four groups that can be obtained from different silyl ketene acetals or enol ethers. At the beginning, an overview on different stereoselective VMARs is presented; disregarding their applications in total syntheses.

M , = 1512.24. orthorhombic. space group P2,2,2,, u = 14.9659(1), h =18.4204(1). c=24.9210(1).& U = 6870.2(1).&', Z = 4 , y,,,,,=1.472g~m-~, F(000) = 3117. !L = 10.11 cm-I. crystal dimensions 0.3 x 0 3x0.4mm. Mo,, radiation (0.71073 A). measurement at 150(2) K. Final R (on F) and wR2 (on F2) were 0 030 and 0 090. respectively, for all 11 760 unique data. Final G O F = 0.95. and the final difference fourier map showed no peak at greater than + 0.891 and less than -0.629 e k 3 . A Flack i parameter of -0.009(8) showed the refinement had been carried out with the correct polarity. 3: C,,H,,DyF,N,,O,,S,. M , = 1570 9X. orthorhombic. space group P 2 , 2 , 2 , , u = 15 7679(4). h = 20.3133(4). ( = 21.7304(4) A, U = 6960.2(3) A'. 2 = 4, pCorr = 1.499 gcm-3. F(000) = 3216. p = 12 55 cm-'. crystal dimensions 0.2 x 0.3 x 0.3 mm. Ma,,radiation (1).71073 A). measurement at 150(2)K Final R (on F ) and 1rR2 (on F 2 ) were 0.042 and 0.1174, respectively, for all 12017 unique data. Final GOF = 1.097. and the final difference fourier map showed no peak at greater than f0.993 and less than -1.088 e k ' . A Flack Y parameter of -0.02119) showed the refinement had been carried out with the correct polarity. Crystal data were collected on a Siemens SMART diffractometer equipped with a CCD (512 x 511 pixels) area detector for all three complexes. The structures were solved by using Patterson methods (SHELXS86) [lo] and refined on F2 using all unique data by full-matrix least-squares (SHELXL93)."" All non-hydrogen atoms have anisotropic displacement parameters with hydrogen atoms generated in ideal positions (riding model). Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CUX-179-152. Copies of the data can be obtained free of charge on application to The Director, CCDC. 12 Union Road, Cambridge CB2 1EZ. U K

Hochdiastereoselektiv verläft die Aldolreaktion der beiden optisch aktiven Bausteine 1, und 2 in der Synthese von Epothilon A. Weiterer Schlüsselschritt dieser Totalsynthese ist eine Ringschlußmetathese. Durch die hohe Konvergenz der Strategie werden viele Alternativen zur Herstellung von – möglicherweise ebenfalls biologisch wirksamen – Analoga eröffnet.