Enantiospecific total synthesis of the sarpagine related indole alkaloids talpinine and talcarpine as well as the improved total synthesis of alstonerine and anhydromacrosalhine-methine via the asymmetric Pictet-Spengler reaction

J Org Chem. 2000 May 19;65(10):3173-91. doi: 10.1021/jo000126e.

Abstract

The enantiospecific total synthesis of talpinine 1 and talcarpine 2 has been accomplished from D-(+)-tryptophan in 13 steps (11 reaction vessels) in 10% and 9.5% overall yields, respectively. Moreover, this synthetic approach has been employed for the improved synthesis of alstonerine 3and anhydromacrosalhine-methine 4 in 12% and 14% overall yield, respectively. A convenient synthetic route for the enantiospecific, stereospecific preparation of the key intermediate (-)-N(a)-H, N(b)-benzyl tetracyclic ketone 15a via the asymmetric Pictet-Spengler reaction on a multihundred-gram scale has been developed. A diastereocontrolled (>30:1) anionic oxy-Cope rearrangement and the intramolecular rearrangement to form ring-E and an N(b)-benzyl/N(b)-methyl transfer reaction also served as key steps. This general approach can now be utilized for the synthesis of macroline/sarpagine related indole alkaloids and their antipodes for biological screening.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / chemical synthesis*
  • Magnetic Resonance Spectroscopy
  • Spectrophotometry, Infrared
  • Stereoisomerism
  • Tryptophan / chemistry

Substances

  • Alkaloids
  • Tryptophan