Cyclotrimerization approach to unnatural structural modifications of pancratistatin and other amaryllidaceae constituents - Synthesis and biological evaluation

Tomas Hudlicky, Michael Moser, Scott C. Banfield, Uwe Rinner, Jean Charles Chapuis, George R. Pettit

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The phenanthridone core of pancratistatin lacking all aromatic oxygenation was prepared by cyclotrimerization of acetylene-containing scaffolds 30 and 41, reflecting the natural and the C-1 epi configuration, respectively, of the amino inositol moiety. The cobalt-catalyzed formation of the aromatic core led to bisTMS derivatives 39 and 48, as well as bisacetyl derivative 51. The effectiveness of cyclotrimerization of the natural or trans series was compared with that of the cis series. In addition, the yields of cyclotrimerization were compared for propargylic amines and propargylic amides. Eleven derivatives, including the fully hydroxylated phenantridone 39, were tested against seven cancer cell lines. Three of the compounds displayed activities only an order of magnitude less than those of 7-deoxypancratistatin. Full experimental and spectral details are provided for all key compounds and future projections for the preparation of unnatural analogs of Amaryllidaceae constituents are advanced, along with some new insight into the minimum pharmacophore of pancratistatin.

Original languageEnglish
Pages (from-to)1313-1337
Number of pages25
JournalCanadian Journal of Chemistry
Volume84
Issue number10
DOIs
Publication statusPublished - Oct 2006

Fingerprint

Derivatives
Acetylene
Oxygenation
Inositol
Cobalt
Amides
Scaffolds
Amines
Cells
pancratistatin
phenanthridone
7-deoxypancratistatin

Keywords

  • Alkaloids
  • Cobalt catalyst
  • Cyclotrimerization

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Organic Chemistry

Cite this

Cyclotrimerization approach to unnatural structural modifications of pancratistatin and other amaryllidaceae constituents - Synthesis and biological evaluation. / Hudlicky, Tomas; Moser, Michael; Banfield, Scott C.; Rinner, Uwe; Chapuis, Jean Charles; Pettit, George R.

In: Canadian Journal of Chemistry, Vol. 84, No. 10, 10.2006, p. 1313-1337.

Research output: Contribution to journalArticle

Hudlicky, Tomas ; Moser, Michael ; Banfield, Scott C. ; Rinner, Uwe ; Chapuis, Jean Charles ; Pettit, George R. / Cyclotrimerization approach to unnatural structural modifications of pancratistatin and other amaryllidaceae constituents - Synthesis and biological evaluation. In: Canadian Journal of Chemistry. 2006 ; Vol. 84, No. 10. pp. 1313-1337.
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