Noncatalytic reaction of isonitriles and carboxylic acids en route to amide-type linkages

Nat Protoc. 2008;3(10):1666-70. doi: 10.1038/nprot.2008.153.

Abstract

This protocol describes the preparation of an N-methyl-asparagine-linked glycosyl amino acid, on the basis of a reaction between carboxylic acids and isonitriles. Under microwave/thermolysis, carboxylic acids can couple with isonitriles without an external catalyst to form N-formyl-amides, which may be further advanced to the corresponding amides, N-methyl amide and N-methyloyl amide. The example reaction of beta-galactopyranosyl isonitrile (7) with a protected aspartic acid under microwave condition in 30 min stereoselectively leads to a beta-galactopyranosyl-N-formyl-asparagine (9). Further chemical transformations readily convert 9 into beta-galactopyranosyl-N-methyl-asparagine (11).

Publication types

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

MeSH terms

  • Amides / chemistry*
  • Carboxylic Acids / chemistry*
  • Hydrogen Bonding
  • Molecular Structure
  • Nitriles / chemistry*

Substances

  • Amides
  • Carboxylic Acids
  • Nitriles