Synthesis and partial biological evaluation of a small library of differentially-linked beta-C-disaccharides

J Org Chem. 2003 Jun 13;68(12):4748-54. doi: 10.1021/jo030039x.

Abstract

The synthesis of a small library of differentially-linked beta-C-disaccharides has been carried out through the use of a radical allylation-RCM strategy. Acids 6 were prepared by Keck allylation of a suitable carbohydrate-based radical precursor, followed by oxidative cleavage of the formed alkene. Dehydrative coupling of these acids with the known olefin alcohol 5 then gave the precursor esters 7 in excellent yield. Methylenation of the esters 7 was followed by RCM and in situ hydroboration-oxidation of the formed glycals to furnish the protected beta-C-disaccharides 10 in good overall yield. Five examples were then deprotected and screened for their efficacy as enzyme inhibitors of beta-glycosidase and against several solid-tumor cell lines for in vitro differential cytotoxicity.

Publication types

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

MeSH terms

  • Combinatorial Chemistry Techniques*
  • Cyclization
  • Disaccharides* / analysis
  • Disaccharides* / chemical synthesis
  • Disaccharides* / pharmacology
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors* / analysis
  • Enzyme Inhibitors* / chemical synthesis
  • Enzyme Inhibitors* / pharmacology
  • Kinetics
  • Molecular Structure
  • Oxidation-Reduction
  • Prunus / chemistry*
  • Stereoisomerism
  • Tumor Cells, Cultured / drug effects
  • beta-Glucosidase / antagonists & inhibitors*

Substances

  • Disaccharides
  • Enzyme Inhibitors
  • beta-Glucosidase