Stereocontrolled synthesis of the northern part of potent proteasome inhibitor TMC-95A

Org Lett. 2001 Sep 6;3(18):2863-5. doi: 10.1021/ol016303v.

Abstract

[reaction: see text]. A protected version of the northern part of TMC-95A, a potent and selective proteasome inhibitor, was synthesized with full stereochemical control. Highlights of this synthesis include (i) a (Z)-selective Mizoroki-Heck reaction to construct the oxyindole portion, (ii) a diastereoselective epoxidation, (iii) a 6-endo selective epoxide opening by Boc carbonyl group to establish the stereochemistry of C6, and (iv) a 1,3-elimination reaction of the L-allo-threonine derivative under Mitsunobu conditions to afford the (Z)-1-propenylamine.

MeSH terms

  • Cysteine Endopeptidases
  • Molecular Conformation
  • Multienzyme Complexes / antagonists & inhibitors
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • Proteasome Endopeptidase Complex

Substances

  • Multienzyme Complexes
  • Peptides, Cyclic
  • Protease Inhibitors
  • TMC-95A
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex