Synthesis and biological activity of [Tic5] didemnin B

Bioorg Med Chem Lett. 1998 Dec 15;8(24):3653-6. doi: 10.1016/s0960-894x(98)00662-3.

Abstract

A didemnin B analog containing a Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) as a conformationally restrained replacement for tyrosine has been synthesized and shown to have comparable potency as a protein biosynthesis inhibitor. Synthetic highlights include an oxidation of an alcohol to an acid in the presence of the sensitive Tic heterocycle and a modified Schmidt-type one-pot macrocyclization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Molecular Structure
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Protein Synthesis Inhibitors / chemical synthesis*
  • Protein Synthesis Inhibitors / chemistry
  • Protein Synthesis Inhibitors / pharmacology*
  • Rabbits
  • Structure-Activity Relationship
  • Tetrahydroisoquinolines*

Substances

  • Isoquinolines
  • Peptides, Cyclic
  • Protein Synthesis Inhibitors
  • Tetrahydroisoquinolines
  • Tic(5) didemnin B