A short synthetic route to (+)-austamide, (+)-deoxyisoaustamide, and (+)-hydratoaustamide from a common precursor by a novel palladium-mediated indole --> dihydroindoloazocine cyclization

J Am Chem Soc. 2002 Jul 10;124(27):7904-5. doi: 10.1021/ja026663t.

Abstract

The first synthesis of (+)-austamide (1), (+)-deoxyisoaustamide (2), and (+)-hydratoaustamide (10) by a very direct route is described (Scheme 1). Starting from tryptophan methyl ester (3) intermediate 5 is generated in two steps in >98% overall yield. The key step in the synthesis is a novel cyclization of 5 involving organopalladium intermediates which gives the dihydroazocine 6. From this key intermediate the target structures are accessible in just a few steps as shown in Scheme 1. The remarkable conversion of 5 --> 6 can be rationalized by the mechanistic pathway shown in Scheme 2 that involves a multistep sequence which includes palladation, cyclization, and rearrangement.

Publication types

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

MeSH terms

  • Azocines / chemistry*
  • Indoles / chemical synthesis*
  • Palladium / chemistry*
  • Stereoisomerism
  • Tryptophan / analogs & derivatives*
  • Tryptophan / chemistry

Substances

  • Azocines
  • Indoles
  • austamide
  • deoxyisoaustamide
  • hydratoaustamide
  • Palladium
  • tryptophan methyl ester
  • Tryptophan