Amino Acids and Peptides. XVII. A Biogenetic-type, Asymmetric Synthesis of (S)-Laudanosine from L-3-(3, 4-Dihydroxyphenyl) alanine by 1, 3-Transfer of Asymmetry

Abstract

The asymmetric synthesis of a representative benzylisoquinoline alkaloid, (S)-(+)-laudanosine (III) was accomplished by means of the biogenetic-type, asymmetric Pictet-Spengler reaction of L-3-(3, 4-dihydroxyphenyl) alanine methyl ester hydrochloride (IV) with sodium (3, 4-dimethoxyphenyl) glycidate (V) (1, 3-asymmetric induction) and the elimination of the chiral center derived from IV (1, 3-transfer of asymmetry). The latter was conveniently achieved by conversion of the cyclized α-amino acid methyl ester (VIa) to the N-benzyl α-amino nitrile (XIII), followed by reductive decyanization with sodium borohydride.