Total synthesis and biological evaluation of Amaryllidaceae alkaloids

Narciclasine, ent-7-deoxypancratistatin, regioisomer of 7-deoxypancratistatin, 10b-epi-deoxypancratistatin, and truncated derivatives

Tomas Hudlicky, Uwe Rinner, David Gonzalez, Hulya Akgun, Stefan Schilling, Peter Siengalewicz, Theodore A. Martinot, George R. Pettit

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

Biocatalytic approaches have yielded efficient total syntheses of the major Amaryllidaceae alkaloids, all based on the key enzymatic dioxygenation of suitable aromatic precursors. This paper discusses the logic of general synthetic design for lycoricidine, narciclasine, pancratistatin, and 7-deoxypancratistatin. Experimental details are provided for the recently accomplished syntheses of narciclasine, ent-7-deoxypancratistatin, and 10b-epi-deoxypancratistatin via a new and selective opening of a cyclic sulfate over aziridines followed by aza-Payne rearrangement. The structural core of 7-deoxypancratistatin has also been degraded to a series of intermediates in which the amino inositol unit is cleaved and deoxygenated in a homologous fashion. These truncated derivatives and the compounds from the synthesis of the unnatural derivatives have been tested against six important human cancer cell lines in an effort to further develop the understanding of the mode of action for the most active congener in this group, pancratistatin. The results of the biological activity testing as well as experimental, spectral, and analytical data are provided in this manuscript for all relevant compounds.

Original languageEnglish
Pages (from-to)8726-8743
Number of pages18
JournalJournal of Organic Chemistry
Volume67
Issue number25
DOIs
Publication statusPublished - Dec 13 2002

Fingerprint

Amaryllidaceae Alkaloids
Derivatives
Aziridines
Inositol
Bioactivity
Sulfates
Cells
Testing
10b-epi-deoxypancratistatin
7-deoxypancratistatin
narciclasine
pancratistatin

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Total synthesis and biological evaluation of Amaryllidaceae alkaloids : Narciclasine, ent-7-deoxypancratistatin, regioisomer of 7-deoxypancratistatin, 10b-epi-deoxypancratistatin, and truncated derivatives. / Hudlicky, Tomas; Rinner, Uwe; Gonzalez, David; Akgun, Hulya; Schilling, Stefan; Siengalewicz, Peter; Martinot, Theodore A.; Pettit, George R.

In: Journal of Organic Chemistry, Vol. 67, No. 25, 13.12.2002, p. 8726-8743.

Research output: Contribution to journalArticle

Hudlicky, Tomas ; Rinner, Uwe ; Gonzalez, David ; Akgun, Hulya ; Schilling, Stefan ; Siengalewicz, Peter ; Martinot, Theodore A. ; Pettit, George R. / Total synthesis and biological evaluation of Amaryllidaceae alkaloids : Narciclasine, ent-7-deoxypancratistatin, regioisomer of 7-deoxypancratistatin, 10b-epi-deoxypancratistatin, and truncated derivatives. In: Journal of Organic Chemistry. 2002 ; Vol. 67, No. 25. pp. 8726-8743.
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