A practical synthesis of (3R,4R)-N-tert-butoxycarbonyl-4-hydroxymethylpyrrolidin-3-ol

Org Biomol Chem. 2007 Sep 7;5(17):2800-2. doi: 10.1039/b708796a. Epub 2007 Jul 20.

Abstract

The title compound (+)-, required for production of transition state analogue inhibitors of enzymes involved in T-cell-dependent disorders, was synthesized in five steps. A 1,3-dipolar cycloaddition of the nitrone formed from formaldehyde and N-benzylhydroxylamine to diethyl maleate gave the racemic cis-isoxazolidine (+/-)-. Reduction of the N-O bond of this compound gave pyrrolidone (+/-)- in excellent yield. A very efficient enzymic resolution of this racemic product led to the title enantiomer (+)-. This route employs only one chromatographic purification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Structure
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / chemistry

Substances

  • N-tert-butoxycarbonyl-4-hydroxymethylpyrrolidin-3-ol
  • Pyrrolidines