Synthesis of chondramide a analogues with modified β-tyrosine and their biological evaluation

Alexander Zhdanko, Anke Schmauder, Christopher I. Ma, L. David Sibley, David Sept, Florenz Sasse, Martin E. Maier

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Starting from cinnamates 9, obtained by Wittig reaction or Heck coupling, the diols 17 were prepared by asymmetric dihydroxylation. This was followed by a regioselective substitution of the 3-OH group with hydrazoic acid under Mitsunobu conditions. Methylation of the 2-OH group and reduction of the azide group led to the β-tyrosine derivatives 8. Condensation with the dipeptide acid 6 furnished the tripeptide part of the chondramides. The derived acids 21 were combined with the hydroxy ester 7 to the esters 22. Cleavage of the tert-butyl groups and intramolecular lactam formation gave rise to the chondramide A analogues 2 b-k. Growth inhibition assays showed most of the analogues to be biologically active. Some of them even reach the activity of jasplakinolide. It can be concluded that the 4-position of the aryl ring in the β-tyrosine of chondramide A tolerates structural modifications quite well.

Original languageEnglish
Pages (from-to)13349-13357
Number of pages9
JournalChemistry - A European Journal
Volume17
Issue number47
DOIs
StatePublished - Nov 18 2011

Keywords

  • Mitsunobu reaction
  • chondramides
  • cyclopeptides
  • total synthesis
  • tyrosine analogues

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