The total synthesis of (-)-callystatin A

Chemistry. 2003 Mar 3;9(5):1129-36. doi: 10.1002/chem.200390130.

Abstract

Callystatin A is a prominent member of a class of natural products which display promising growth inhibition of cancer cells in their biological profile. The challenging structure and the interesting biological activity of (-)-callystatin A fueled our interest in the synthesis of this marine natural product. We achieved the total synthesis using a highly convergent approach joining four subunits together with a Wittig olefination, a selective Heck reaction and an aldol reaction as the pivotal steps. The aldol reaction as one of the final transformations during the synthesis opens fast access to a variety of structural analogues and circumvents tedious protecting group manipulations. Here we report an improved synthesis utilizing a modified vinyl iodide which shortens the synthesis by two steps. Additionally, first biological results will be reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Cell Death / drug effects
  • Cell Division / drug effects
  • Cytotoxins / chemical synthesis
  • Fatty Acids, Unsaturated / chemical synthesis*
  • Fatty Acids, Unsaturated / pharmacology
  • Humans
  • Jurkat Cells
  • Porifera / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Cytotoxins
  • Fatty Acids, Unsaturated
  • callystatin A