O-sialylation with N-acetyl-5-n,4-o-carbonyl-protected thiosialoside donors in dichloromethane: facile and selective cleavage of the oxazolidinone ring

J Org Chem. 2007 Mar 30;72(7):2387-91. doi: 10.1021/jo062431r. Epub 2007 Mar 6.

Abstract

An N-acetyl-5-N,4-O-carbonyl-protected thiosialoside donor, the structure of which has been defined through X-ray crystallography, was prepared and tested in couplings to a wide range of acceptors. This donor gives excellent yields and alpha-selectivities in linking with various primary alkyl and carbohydrate acceptors under the N-iodosuccinimide and trifluoromethanesulfonic acid in situ activation method at -40 degrees C in dichloromethane. The favorable affect of the oxazolidinone substructure for alpha-sialylation is illustrated by a comparison study with a N,N-diacetylsialyl donor, which exhibited inferior yields and alpha-selectivities. The sialylation selectivity is independent of the anomeric configuration of the donor, but is highly related to the reaction temperature under the NIS/TfOH activation method. In contrast to the NIS/TfOH method, the Ph2SO/Tf2O promotion gives beta-selective couplings in dichloromethane. The oxazolidinone of the N-acetyl-5-N,4-O-carbonyl protected sialosides, both alpha- and beta-anomers, could be cleaved cleanly by treatment with sodium methoxide under mild conditions without removal of the acetamide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Furans / chemistry*
  • Gangliosides / chemistry*
  • Methyl Chloride / chemistry*
  • Molecular Structure
  • N-Acetylneuraminic Acid / chemistry*
  • Oxazolidinones / chemistry*

Substances

  • Furans
  • Gangliosides
  • Oxazolidinones
  • Methyl Chloride
  • N-Acetylneuraminic Acid