Synthesis of the Bis-Spiroacetal Core of the Antimitotic Agent Spirastrellolide B

J Org Chem. 2011 Nov 18;76(22):9417-28. doi: 10.1021/jo201729t. Epub 2011 Oct 20.

Abstract

The spirastrellolides are a family of potent antimitotic agents isolated from the marine sponge Spirastrella coccinea . Synthetic studies toward the DEF bis-spiroacetal core of spirastrellolide B are reported. A modular approach was pursued by the use of two dithiane disconnections to enable a highly convergent synthesis. The ease of lithiation and nucleophilicity of these 2-substituted-1,3-dithianes were investigated during the course of the synthesis, and the alkylations were found to proceed most efficiently at elevated temperatures. Formation of the [5,6,6]-bis-spiroacetal ring system was achieved via a double dithiane deprotection/spiroacetalization strategy.

MeSH terms

  • Alkylation
  • Antimitotic Agents / chemical synthesis*
  • Antimitotic Agents / chemistry
  • Antimitotic Agents / isolation & purification
  • Biological Products / chemical synthesis*
  • Biological Products / chemistry
  • Macrolides / chemical synthesis*
  • Macrolides / chemistry
  • Macrolides / isolation & purification
  • Molecular Structure
  • Quinolizines / chemistry*
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / isolation & purification
  • Sulfur Compounds / chemistry*

Substances

  • Antimitotic Agents
  • Biological Products
  • Macrolides
  • Quinolizines
  • Spiro Compounds
  • Sulfur Compounds
  • dithiane
  • spirastrellolide B