Formal total synthesis of (+)-salicylihalamides A and B: a combined chiral pool and RCM strategy

J Org Chem. 2003 Dec 26;68(26):10030-9. doi: 10.1021/jo0301550.

Abstract

The formal total synthesis of the (+)-salicylihalamides A and B is detailed, utilizing a chiral pool approach to generate the three stereogenic centers and a ring-closing metathesis (RCM) for the formation of the macrocyclic ring structure. Starting from a known glucose-derived alcohol, the formal total synthesis was achieved in an efficient 13-step protocol in 26% overall yield. It was found that substitution at the remote phenolic group significantly influenced the ratio of the E- and Z-double bond products in the RCM step. The introduction of phenol protecting groups provided E-isomers preferentially and also enhanced the rates of the RCM reactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Catalysis
  • Cyclization
  • Organomercury Compounds / chemistry
  • Phenols / chemistry
  • Ruthenium / chemistry
  • Stereoisomerism

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Organomercury Compounds
  • Phenols
  • salicylihalamide A
  • Ruthenium