Highly efficient and concise synthesis of both antipodes of SB204900, clausenamide, neoclausenamide, homoclausenamide and zeta-clausenamide. Implication of biosynthetic pathways of Clausena alkaloids

Org Biomol Chem. 2009 Jun 21;7(12):2628-34. doi: 10.1039/b901965k. Epub 2009 May 5.

Abstract

The synthesis of both antipodes of N-methyl-N-[(Z)-styryl]-3-phenyloxirane-2-carboxamide (SB204900), clausenamide, neoclausenamide, homoclausenamide and zeta-clausenamide have been accomplished using (2S,3R)- and (2R,3S)-3-phenyloxirane-2-carboxamides as the starting materials, and SB204900 was found to be a common precursor to other N-heterocyclic clausena alkaloids. Mediated by Brønsted acids under different conditions, for example, SB204900 underwent efficient and diverse alkene-epoxide cyclization, enamide-epoxide cyclization and arene-epoxide cyclization reactions to produce the five-membered N-heterocyclic neoclausenamide, its 6-epimer, the six-membered N-heterocyclic homoclausenamide and the eight-membered N-heterocyclic zeta-clausenamide, respectively, in good to excellent yields. Regiospecific oxidation of neoclausenamide and its 6-epimer afforded neoclausenamidone. Enolization of neoclausenamidone in the presence of LiOH and the subsequent protonation under kinetic conditions at -78 degrees C led to the epimerization of neoclausenamidone into clausenamidone. Reduction of clausenamidone using NaBH(4) furnished clausenamide in high yield.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / biosynthesis
  • Alkaloids / chemical synthesis*
  • Biomimetics*
  • Clausena / metabolism*
  • Ethylene Oxide / chemistry
  • Lactams / chemical synthesis*
  • Lactones / chemical synthesis*
  • Lactones / metabolism
  • Lignans / biosynthesis
  • Lignans / chemical synthesis*
  • Pyridones / chemical synthesis*
  • Pyridones / metabolism
  • Stereoisomerism

Substances

  • Alkaloids
  • Lactams
  • Lactones
  • Lignans
  • Pyridones
  • homoclausenamide
  • clausenamide
  • SB 204990
  • Ethylene Oxide