Rychnovsky polyol synthesis

Rychnovsky and his group have recently developed new synthetic methods that lead to the total syntheses of the polyene macrolides roxaticin [2], roflamycoin [3], and filipin III [4]. The polyol chains of all three natural products were constructed by iterative, stereoselective alkylation of lithiated cyanohydrin acetonides and subsequent reductive decyanation, illustrated here by the synthesis of the polyol framework of filipin III (1) (Scheme I). The bifunctional cyanohydrin acetonide 2, prepared by ruthenium/BINAP catalyzed enantioselective hydrogenation of the corresponding ) -keto ester (BINAP = [ 1,1 -binaphthyl]-2,2 -diylbis(diphenylphosphane)), is deprotonated with LiNEt2 and alkylated with 2-benzyloxy-l-iodoethane. The alkylation product 3 is converted by a Finkelstein reaction into the iodide 4, which is used to alkylate a second... 

Scheme 1. Synthesis of the C(1)-C(I5) polyol fragment 8b of filipin 111 (1) according to Rychnovsky et al. Bn = henzyl, TBS = terf-hutyldimethylsilyl.

SCHEME 2.161 Synthesis of dibromide fragment 183 and completion of the polyol fragment in the synthesis of roxatidn hy Rychnovsky. 

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