Electrocyclic ring-opening/pi-allyl cation cyclization reaction sequences involving gem-dihalocyclopropanes as substrates: application to syntheses of (+/-)-, (+)-, and (-)-gamma-lycorane

J Org Chem. 2000 Jul 14;65(14):4241-50. doi: 10.1021/jo991791u.

Abstract

The readily prepared gem-dibromocyclopropanes (+/-)-13 and (+/-)-19 each engage in a silver(I)-promoted electrocyclic ring-opening/pi-allyl cation cyclization sequence to deliver the hexahydroindole (+/-)-20, which participates in a Suzuki cross-coupling reaction with arylboronic acid 3 to give the tetracyclic compound (+/-)-21. Catalytic hydrogenation of this last compound proceeds in a completely stereoselective manner to give the saturated analogue (+/-)-24, which undergoes Bischler-Napieralski cyclization on reaction with phosphorus oxychloride. The resulting lactam (+/-)-25 is then reduced with lithium aluminum hydride to give (+/-)-gamma-lycorane [(+/-)-1]. By using (-)-menthyl-derived carbamates 27 and 28, this chemistry has been extended to the synthesis of the (+)- and (-)-modifications of the title compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Amaryllidaceae Alkaloids*
  • Animals
  • Carbohydrate Conformation
  • Cyclopropanes / chemical synthesis*
  • Disaccharides / chemical synthesis*
  • Disaccharides / chemistry
  • Disaccharides / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Fucosyltransferases / antagonists & inhibitors*
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Humans
  • Kinetics
  • Models, Molecular
  • Molecular Conformation

Substances

  • Alkaloids
  • Amaryllidaceae Alkaloids
  • Cyclopropanes
  • Disaccharides
  • Enzyme Inhibitors
  • lycorane
  • Fucosyltransferases
  • galactoside 3-fucosyltransferase
  • Glycoside Hydrolases