A tandem metal carbene cyclization-cycloaddition approach to the pseudolaric acids

J Org Chem. 2003 May 30;68(11):4195-205. doi: 10.1021/jo026399m.

Abstract

An approach toward the synthesis of the antifungal and cytotoxic pseudolaric acids based on the tandem metal carbene cyclization-cycloaddition reaction is described. Using this strategy, the advanced intermediate 3a bearing three of the four stereocenters of the target molecules has been synthesized. The substrate-controlled diastereoselectivity of the tandem carbene cyclization-cycloaddition was preferential for the undesired diastereomer, but reagent control through the use of Hashimoto's chiral rhodium catalyst Rh(2)(S-BPTV)(4) reversed the selectivity in favor of 3a. Ring opening of the oxabicyclic nucleus to give a hydroxycycloheptene has been demonstrated in a model study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Catalysis
  • Combinatorial Chemistry Techniques*
  • Cyclization
  • Diterpenes / chemical synthesis*
  • Diterpenes / pharmacology
  • Hydrocarbons
  • Indicators and Reagents
  • Methane / analogs & derivatives*
  • Methane / chemistry*
  • Models, Molecular*
  • Stereoisomerism

Substances

  • Antifungal Agents
  • Antineoplastic Agents
  • Diterpenes
  • Hydrocarbons
  • Indicators and Reagents
  • carbene
  • pseudolaric acid B
  • pseudolaric acid A
  • Methane