Convergent and enantiospecific total syntheses of rifamycin W ansa-chain compound (48) and erythronolide A (61) were achieved by the use of a “two-stage coupling” process, which was developed for stereocontrolling the carbon chain connections in the synthesis. The new coupling process consists of the first stage of addition reaction of appropriate vinyllithio compounds to 2 methyl-substituted aldehydes and the second stage of homogeneous hydrogenation with Wilkinson's catalyst of the major “Cram” type of addition products. In the practical total syntheses of 48 and 61, the process gave predominantly “Cram” (syn)- anti type of coupling products to provide the proper chiral sequences of 48 and (9S)-9-dihydroerythronolide A which was an important precursor of 61. Principal stereochemical features of this process are described for using it effectively in natural product synthesis.
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