Chemoenzymatic synthesis of amaryllidaceae constituents and biological evaluation of their C-1 analogues. the next generation synthesis of 7-deoxypancratistatin and trans -dihydrolycoricidine

Jonathan Collins, Uwe Rinner, Michael Moser, Tomas Hudlicky, Ion Ghiviriga, Anntherese E. Romero, Alexander Kornienko, Dennis Ma, Carly Griffin, Siyaram Pandey

Research output: Contribution to journalArticle

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Abstract

An efficient synthesis of C-1 derivatives of 7-deoxypancratistatin is reported. The key steps include the following: selective opening of an epoxide with aluminum acetylide in the presence of an aziridine; solid-state silica-gel-catalyzed opening of an aziridine; and oxidative cleavage of a phenanthrene core and its recyclization to phenanthridone to provide the key C-1 aldehyde 22. The conversion of this aldehyde to C-1 acetoxymethyl and C-1 hydroxymethyl derivatives is described along with the evaluation of their biological activity against several cancer cell lines and in an apoptosis study. The C-1 acetoxymethyl derivative has shown promising activity comparable to that of the natural product. In addition, a total synthesis of trans-dihydrolycoricidine and a formal total synthesis of 7-deoxypancratistatin are reported from aldehyde 22. Detailed experimental and spectral data are provided for all new compounds.

Original languageEnglish
Pages (from-to)3069-3084
Number of pages16
JournalJournal of Organic Chemistry
Volume75
Issue number9
DOIs
Publication statusPublished - May 7 2010

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Aldehydes
Derivatives
Epoxy Compounds
Silica Gel
Bioactivity
Biological Products
Aluminum
Cells
Apoptosis
7-deoxypancratistatin
trans-dihydrolycoricidine
aziridine
phenanthridone
phenanthrene

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Chemoenzymatic synthesis of amaryllidaceae constituents and biological evaluation of their C-1 analogues. the next generation synthesis of 7-deoxypancratistatin and trans -dihydrolycoricidine. / Collins, Jonathan; Rinner, Uwe; Moser, Michael; Hudlicky, Tomas; Ghiviriga, Ion; Romero, Anntherese E.; Kornienko, Alexander; Ma, Dennis; Griffin, Carly; Pandey, Siyaram.

In: Journal of Organic Chemistry, Vol. 75, No. 9, 07.05.2010, p. 3069-3084.

Research output: Contribution to journalArticle

Collins, Jonathan ; Rinner, Uwe ; Moser, Michael ; Hudlicky, Tomas ; Ghiviriga, Ion ; Romero, Anntherese E. ; Kornienko, Alexander ; Ma, Dennis ; Griffin, Carly ; Pandey, Siyaram. / Chemoenzymatic synthesis of amaryllidaceae constituents and biological evaluation of their C-1 analogues. the next generation synthesis of 7-deoxypancratistatin and trans -dihydrolycoricidine. In: Journal of Organic Chemistry. 2010 ; Vol. 75, No. 9. pp. 3069-3084.
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abstract = "An efficient synthesis of C-1 derivatives of 7-deoxypancratistatin is reported. The key steps include the following: selective opening of an epoxide with aluminum acetylide in the presence of an aziridine; solid-state silica-gel-catalyzed opening of an aziridine; and oxidative cleavage of a phenanthrene core and its recyclization to phenanthridone to provide the key C-1 aldehyde 22. The conversion of this aldehyde to C-1 acetoxymethyl and C-1 hydroxymethyl derivatives is described along with the evaluation of their biological activity against several cancer cell lines and in an apoptosis study. The C-1 acetoxymethyl derivative has shown promising activity comparable to that of the natural product. In addition, a total synthesis of trans-dihydrolycoricidine and a formal total synthesis of 7-deoxypancratistatin are reported from aldehyde 22. Detailed experimental and spectral data are provided for all new compounds.",
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