Synthesis, resolution, and absolute stereochemistry of (-)-blestriarene C

J Org Chem. 2003 Mar 21;68(6):2099-108. doi: 10.1021/jo026747k.

Abstract

A naturally occurring 1,1'-biphenanthrene, blestriarene C (1), was prepared in 13 steps and 30% overall yield. The key steps are the ester-mediated nucleophilic aromatic substitution on 2,6-di-tert-butyl-4-methoxyphenyl 5-isopropoxy-2-methoxybenzoate (4) by 2-methoxy-4-methoxymethoxy-6-methylphenylmagnesium bromide (5) and a novel intramolecular cyclization of the resulting 4-isopropoxy-2'-methoxy-4'-methoxymethoxy-6'-methylbiphenyl-2-carboxylic ester 14 to 7-isopropoxy-4-methoxy-2-(methoxymethoxy)phenanthren-9-ol (15). The racemic blestriarene C was optically resolved by chiral HPLC on a preparative scale to give several 10-mg yields of both the enantiomers in up to 95% ee. The absolute stereochemistry was determined to be S(a)-(-) by the axial chirality recognition method, which was based on the stereospecific formation of a 12-membered cyclic diester containing two biaryl-o,o'-diyl unites joined by ester -CO(2)- linkages. The validity of the method was confirmed by an X-ray crystallographic analysis and ab initio conformational analyses of such 12-membered cyclic diesters. It was found that blestriarene C and its 7,7'-diisopropyl ether 2 underwent rapid photoracemization even under ambient light exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • Crystallography, X-Ray
  • Molecular Conformation
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Phenanthrenes* / analysis
  • Phenanthrenes* / chemical synthesis
  • Phenanthrenes* / chemistry*
  • Stereoisomerism
  • Stilbenes*

Substances

  • 1,1'-biphenanthrene
  • Phenanthrenes
  • Stilbenes
  • blestriarene C