Total synthesis of an antitumor agent, mucocin, based on the "chiron approach"

J Org Chem. 2002 Aug 9;67(16):5739-52. doi: 10.1021/jo020211h.

Abstract

The total synthesis of a powerful antitumor acetogenin, mucocin (1), was achieved through a palladium-catalyzed cross-coupling reaction of the THP-THF fragment 2 and a terminal butenolide 3. The key process for construction of the fragment 2 was chelation-controlled addition of ethynylmagnesium chloride to disilyl aldehyde 23a and condensation of the alkyllithium prepared therefrom with THP aldehyde 4 in the presence of CeCl(3). Synthesis of the lactone 3 relied on a novel approach by taking advantage of a radical cyclization of acyclic selenocarbonate 6. The three building blocks 4, 5a, and 6 were prepared stereoselectivly from D-galactose (7), 2,5-anhydro-D-mannitol (8), and L-rhamnose (9), respectively. A new and efficient method for desymmetrization of the C(2)-symmetrical compound 8 is also described.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Indicators and Reagents
  • Isomerism
  • Lactones / chemical synthesis*
  • Lactones / chemistry*
  • Molecular Conformation
  • Pyrans / chemical synthesis*
  • Pyrans / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Indicators and Reagents
  • Lactones
  • Pyrans
  • mucocin