Synthesis of 10b(R)-hydroxypancratistatin, 10b(S)-hydroxy-1-epipancratistatin, 10b(S)-hydroxy-1,2-diepipancratistatin and related isocarbostyrils

George Pettit, Noeleen Melody, Delbert L. Herald, Jean M. Schmidt, Robin Pettit, Jean Chapuis

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Narciclasine (2) was transformed by a series of reactions where Sharpless asymmetric hydroxylations served as the stereochemical controlling step to 10b(R)-hydroxypancratistatin (3), 10b(S)-hydroxy-1-epipancratistatin (13) and 10b(S)-hydroxy-1,2-diepipancratistatin (16). Synthesis of 10b(S)-hydroxy-1,2-diepipancratistatin (16) proceeded from α-triol (11) via cyclic sulfate (14) and inversion of C-2 with cesium benzoate followed by saponification and treatment with a catalytic amount of acid. Compared to pancratistatin (1), these structural modifications led to decreased cancer cell growth inhibition against a minipanel of human cancer cell lines. Narciclasine (2) inhibited the pathogenic yeast Cryptococcus neoformans, and modifications (4, 14 and 15) inhibited growth of the pathogenic bacterium Neisseria gonorrhoeae.

Original languageEnglish (US)
Pages (from-to)139-155
Number of pages17
JournalHeterocycles
Volume56
Issue number1-2
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

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