Syntheses of novel 4-tert-alkyl ether proline-based 16- and 17-membered macrocyclic compounds

J Org Chem. 2002 Apr 19;67(8):2730-3. doi: 10.1021/jo020075g.

Abstract

Starting from N-Cbz-4-hydroxyproline methyl ester 1, a boron trifluoride-diethyl etherate-catalyzed reaction provided 4-tert-alkyl ether proline 4. Two deprotections and amide bond formations furnished the phenol alcohol 2. The macrocyclization of 2 was accomplished through a Mitsunobu reaction using triphenylphosphine and 1,1'-(azodicarbonyl)dipiperidine (ADDP), to afford novel 16- and 17-membered proline-based macrocyclic compounds of type 3.

MeSH terms

  • Combinatorial Chemistry Techniques / methods
  • Drug Design
  • Heterocyclic Compounds / chemical synthesis*
  • Hydroxyproline / analogs & derivatives
  • Hydroxyproline / chemical synthesis*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis*
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds
  • N-Cbz-4-hydroxyproline methyl ester
  • Proline
  • Hydroxyproline