A strategy for the solution-phase parallel synthesis of N-(pyrrolidinylmethyl)hydroxamic acids

J Org Chem. 2000 Jun 16;65(12):3811-5. doi: 10.1021/jo000186k.

Abstract

Both five- and six-membered iminocyclitols have proven to be useful transition-state analogue inhibitors of glycosidases. They also mimic the transition-state sugar moiety of the nucleoside phosphate sugar in glycosyltransferase-catalyzed reactions. Described here is the development of a general strategy toward the parallel synthesis of a five-membered iminocyclitol linked to a hydroxamic acid group designed to mimic the transition state of GDP-fucose complexed with Mn(II) in fucosyltransferase reactions. The iminocyclitol 8 containing a protected hydroxylamine unit was prepared from D-mannitol. The hydroxamic acid moiety was introduced via the reaction of 8 with various acid chlorides. The strategy is generally applicable to the construction of libraries for identification of glycosyltransferase inhibitors.

Publication types

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

MeSH terms

  • Fucosyltransferases / chemistry
  • Fucosyltransferases / metabolism
  • Guanosine Diphosphate Fucose / chemistry
  • Guanosine Diphosphate Fucose / metabolism
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / chemistry
  • Indicators and Reagents
  • Manganese / chemistry
  • Manganese / metabolism
  • Mannitol
  • Molecular Conformation
  • Molecular Structure
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / chemistry
  • Solutions

Substances

  • Hydroxamic Acids
  • Indicators and Reagents
  • Pyrrolidines
  • Solutions
  • Guanosine Diphosphate Fucose
  • Mannitol
  • Manganese
  • Fucosyltransferases