2. Academic Validation
  3. Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues

Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues

  • J Med Chem. 2009 Jan 22;52(2):238-40. doi: 10.1021/jm8013579.
Ranganathan Balasubramanian 1,  Bhooma Raghavan,  Adrian Begaye,  Dan L Sackett,  Robert A Fecik
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, 308 Harvard Street SE, 8-101 Weaver-Densford Hall, University of Minnesota, Minneapolis, Minnesota 55455-0353, USA.
PMID: 19102699 DOI: 10.1021/jm8013579
Abstract

A stereoselective total synthesis of the cytotoxic Natural Products tubulysin U, tubulysin V, and its unnatural epimer epi-tubulysin V, is reported. Simplified analogues containing N,N-dimethyl-D-alanine as a replacement for the N-terminal N-Me-pipecolinic acid residue of the tubulysins are also disclosed. Biological evaluation of these Natural Products and analogues provided key information with regard to structural and stereochemical requirements for antiproliferative activity and tubulin polymerization inhibition.

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