A biomimetic total synthesis of (-)-spirotryprostatin B and related studies

J Org Chem. 2000 Jul 28;65(15):4685-93. doi: 10.1021/jo000306o.

Abstract

The prenylated natural products spirotryprostatin A and B derived from the Trp-Pro diketopiperazine also feature an oxidative rearrangement of the indole to form a spirooxindole. Synthetically, formation of the oxindole ring was stereoselectively accomplished by reaction of the appropriate indole precursor with N-bromosuccinimide. For optimum results, the oxidation should be carried out prior to diketopiperazine cyclization. In this manner, we have synthesized the tetrahydro- and dihydro- analogues of spirotryprostatin B in four steps from L-tryptophan methyl ester. The dihydro derivative was then converted to spirotryprostatin B by unsaturation of the pyrrolidine ring to a pyrroline, thus unambiguously confirming the structure of the natural product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Aspergillus fumigatus / chemistry*
  • Cell Cycle / drug effects
  • Cyclization
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tryptophan / analogs & derivatives
  • Tryptophan / metabolism

Substances

  • Alkaloids
  • Piperazines
  • Spiro Compounds
  • demethoxyfumitremorgin C
  • spirotryprostatin B
  • tryptophan methyl ester
  • Tryptophan