Asymmetric synthesis and absolute configuration of (-)-trypargine.

An asymmetric synthesis of (1S)-(-)-trypargine (1a) was accomplished. The Pictet-Spengler condensation of (+)-Nb-benzyl-D-tryptophan methyl ester ((+)-3) with α-ketoglutaric acid, followed by methylation of the resulting monocarboxylic acid ((-)-4a), provided (1S, 3R)-(-)-methyl 2-benzyl-3-methoxycarbonyl-1, 2, 3, 4-tetrahydro-9H-pyrido [3, 4-b] indole-1-propionate ((-)-6a), which was converted into (-)-trypargine (1a). The absolute configuration of natural trypargine (1a) at the C-1 position was determined to be S.