A practical entry to β-aryl-β-alkyl amino alcohols: application to the synthesis of a potent BACE1 inhibitor

Org Biomol Chem. 2012 Sep 7;10(33):6758-66. doi: 10.1039/c2ob25845e. Epub 2012 Jul 19.

Abstract

The 1,2-addition of alkyl Grignard reagents to readily available N-tert-butanesulfinyl ketimines, bearing an α-silyloxy substituent, proceeds in high yields and excellent diastereocontrol. The utility of the present method was demonstrated by the synthesis, in enantiomerically pure form, of one recently disclosed β-secretase (BACE1) inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Amino Alcohols / chemical synthesis*
  • Amino Alcohols / chemistry
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Humans
  • Imines / chemical synthesis
  • Imines / chemistry
  • Nitriles / chemical synthesis
  • Nitriles / chemistry

Substances

  • Amino Alcohols
  • Enzyme Inhibitors
  • Imines
  • Nitriles
  • ketimine
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human