Synthesis of B-ring-modified steroids through BF3-promoted rearrangement/substitution of 6β-hydroxy-5,19-cyclosteroids

Org Lett. 2012 Jul 20;14(14):3692-5. doi: 10.1021/ol301532w. Epub 2012 Jul 5.

Abstract

The BF3·Et2O-promoted reaction of 3β-acetoxy-5,19-cyclo-pregnan-6β-ol-20-one with different nucleophiles was investigated. B-homo steroids (3β-acetoxy-B-homo-6a-β-alkoxy-pregna-5(10)-en-20-ones) were obtained with primary and secondary alcohols, while the reaction with common carboxylic acids selectively afforded the corresponding 3β-acetoxy-6β-(acyloxymethyl)-pregna-5(10)-en-20-ones. The transformations are supposed to proceed via the rearrangement of a cyclopropyl-methyl cation (bicyclobutonium) intermediate, which is regioselectively opened in dependence on the nucleophile employed. The method represents an efficient, diversity-oriented entry to new B-ring-modified steroids, which are of potential pharmaceutical relevance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boranes / chemistry*
  • Carboxylic Acids / chemistry
  • Cyclosteroids / chemical synthesis*
  • Cyclosteroids / chemistry
  • Molecular Structure
  • Pregnenolone / chemistry*
  • Steroids / chemistry*

Substances

  • 3beta-acetoxy-5,19-cyclo-pregnan-6beta-ol-20-one
  • 6beta-hydroxy-5,19-cyclosteroid
  • Boranes
  • Carboxylic Acids
  • Cyclosteroids
  • Steroids
  • Pregnenolone
  • boron trifluoride