Oudemansins synthesis

Ester homologation (11, 104).2 In an improved method for ester homologation via an a-bromo-a-keto dianion, an ester (RCO Hs) is treated sequentially with LiCHBr2, LiTMP (1 equiv.), and then an excess of BuLi to provide RC=C—OLi. Rearrangement occurs with complete retention of stereochemistry. This method provides a stereospecific synthesis of the antibiotic oudemansin (2). 

This methodology has been applied to the synthesis of oudemansins by Kallmerten. In this example, the Wittig alkenation gave mixtures of ( )- and (Z)-products, as well as epimerizing the ether position. These problems were solved by acylating the phosphine oxide (239) and carrying out reduction and... 

In the 1980s, Hiroyuki Akita and Takeshi Oishi published an enantioselective synthesis of oudemansin A, where a jS-keto-ester is reduced stereoselectively to the jS-hydroxy-ester with Candida albicans. After chromatographic purification from small amounts of diastereomers, the ester is then homologised in a classical reduction and cyanide substitution sequence. The remainder of the synthesis for establishing the acrylate system follows the previously described methodology. [53-55]... 

Nakata T, Kuwabara T, Tani T, Oishi T (1982) Total synthesis of (+)-oudemansin. Tetrahedron Lett 23 1015-1016 Nambiar KP, Stauffer DM, Kolodziej PA, Benner SA (1983) A mechanistic basis for the stereoselectivity of enzymatic transfer of hydrogen from nicotinamide cofactors. J Am Chem Soc 105 5886-5890 Ng GY, Yuan L-C, Jakovac IJ, Jones JB (1984) Enzymes in organic synthesis. 29. Preparations of enantiomerically pure cis-2,3- and 2,4-dimethyl lactones via horse liver alcohol dehydrogenase-catalyzed oxidations. Tetrahedron 40 1235-1243 Oae S, Nagata T, Yoshimura T, Fujimori K (1982) Reduction of diaryl disulfides with 1-benzyl-1,4-dihydronicotinamide. Tetrahedron Lett 3189-3192... 

The first total synthesis of (-)-oudemansin 108 has been achieved using, as a chiral pool starting material, L-quebrachitol. This chemistry not only illustrates the synthetic versatility of cyclitols, but also served to establish the absolute stereochemistry of 108 (sugar numbering shown). 

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