Solid-phase synthesis of a branched hexasaccharide using a highly efficient synthetic strategy

J Org Chem. 2001 Dec 14;66(25):8540-8. doi: 10.1021/jo016018p.

Abstract

The solid-phase synthesis of branched lacto-N-neohexaose derivative 1 occurring in human milk is described. The new building block of lactose 3 bearing the orthogonal temporary hydroxy protecting groups 9-fluorenylmethyloxycarbonyl (Fmoc) and levulinoyl (Lev) has been prepared. Its use, together with that of lactosamine donor 4, glucosamine donor 5, and O-galactosyl trichloroacetimidate 6, has enabled the preparation of hexasaccharide 22 following two different approaches in excellent overall yield (43%, 90% per step over eight steps). An additional key feature of this work is the successful use of newly prepared ester-type linker 2, having a benzylic spacer connected to the anomeric oxygen. This linker presents the advantage of producing a benzylic anomeric moiety after cleavage from the polymer support, which could be easily removed to obtain the unprotected oligosaccharide 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Sequence
  • Cross-Linking Reagents
  • Esters / chemistry
  • Fluorenes / chemistry
  • Glucosamine / chemistry
  • Lactose / chemistry
  • Milk, Human / chemistry
  • Molecular Sequence Data
  • Oligosaccharides / chemical synthesis*

Substances

  • Cross-Linking Reagents
  • Esters
  • Fluorenes
  • Oligosaccharides
  • 1-(9-fluorenyl)methyl chloroformate
  • Lactose
  • Glucosamine