Ring opening of pymisyl-protected aziridines with organocuprates

Chemistry. 2010 Nov 2;16(41):12474-80. doi: 10.1002/chem.201001026.

Abstract

The pyrimidine-2-sulfonyl (pymisyl) group is introduced as a new protecting group that can be used to activate aziridines towards ring opening. It is readily introduced and removed under mild conditions. Regioselective ring opening of pymisyl-protected 2-methyl-aziridine with organocuprates gives the corresponding sulfonamides in high yields, and the pymisyl group can subsequently be removed upon treatment with a thiolate. The versatility of this new nitrogen protecting group is illustrated with a new synthesis of Selegiline, a monoamine oxidase-B inhibitor marketed for the treatment of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aziridines / chemical synthesis*
  • Aziridines / chemistry
  • Combinatorial Chemistry Techniques
  • Copper / chemistry*
  • Molecular Structure
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Organometallic Compounds / chemistry*
  • Parkinson Disease / drug therapy*
  • Selegiline / chemical synthesis*
  • Selegiline / chemistry
  • Selegiline / pharmacology
  • Stereoisomerism
  • Sulfhydryl Compounds / chemistry
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry

Substances

  • Aziridines
  • Monoamine Oxidase Inhibitors
  • Organometallic Compounds
  • Sulfhydryl Compounds
  • Sulfonamides
  • Selegiline
  • Copper
  • Monoamine Oxidase