Stereochemical studies. LIII. An asymmetric synthesis of (3S 15S 20R)-yohimbone from L-tryptophan by 1,3-transfer of asymmetry.

Abstract

The asymmetric synthesis of (3S 15S 20R)-(-)-yohimbone (III) was accomplished. The key reactions in the process are : (i) the asymmetric Pictet-Spengler reaction of L-tryptophan (IV) with sodium 3-(m-methoxyphenyl) glycidate (V) (1, 3-asymmetric induction), and (ii) the elimination of the chiral center derived from IV (1, 3-transfer of asymmetry). The latter was conveniently achieved by converting the cyclic α-amino acid amide (XIIIa) to the pentacyclic α-amino nitrile (XIV), followed by reductive decyanization with sodium borohydride. Thus, the indole alkaloids, natural yohimbol (XX) and natural corynantheine (XXI), may be synthesized from L-tryptophan.