Enantioselective total synthesis of (-)-triptolide, (-)-triptonide, (+)-triptophenolide, and (+)-triptoquinonide

J Org Chem. 2000 Apr 7;65(7):2208-17. doi: 10.1021/jo9919613.

Abstract

The first enantioselective total synthesis of (-)-triptolide (1), (-)-triptonide (2), (+)-triptophenolide (3), and (+)-triptoquinonide (4) was completed. The key step involves lanthanide triflate-catalyzed oxidative radical cyclization of (+)-8-phenylmenthyl ester 30 mediated by Mn(OAc)3, providing intermediate 31 with good chemical yield (77%) and excellent diastereoselectivity (dr 38:1). (+)-Triptophenolide methyl ether (5) was then prepared in > 99% enantiomeric excess (> 99% ee), and readily converted to natural products 1-4. In addition, transition state models were proposed to explain the opposite chiral induction observed in the oxidative radical cyclization reactions of chiral beta-keto esters 17 (without an alpha-substituent) and 17a (with an alpha-chloro substituent).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Cyclization
  • Diterpenes / chemical synthesis*
  • Drugs, Chinese Herbal / chemistry*
  • Epoxy Compounds
  • Phenanthrenes*
  • Stereoisomerism
  • Triterpenes / chemical synthesis*

Substances

  • Diterpenes
  • Drugs, Chinese Herbal
  • Epoxy Compounds
  • Phenanthrenes
  • Triterpenes
  • triptoquinonide
  • triptolide
  • triptonide
  • triptophenolide