Chemoenzymatic Synthesis of Amaryllidaceae Constituents and Biological Evaluation of their C-1 Analogues. The Next Generation Synthesis of 7-Deoxypancratistatin and trans-Dihydrolycoricidine
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- 作者：Jonathan Collins ; Uwe Rinner ; Michael Moser ; Tomas Hudlicky ; Ion Ghiviriga ; Anntherese E. Romero ; Alexander Kornienko ; Dennis Ma ; Carly Griffin ; Siyaram Pandey
- 刊名：Journal of Organic Chemistry
- 出版年：2010
- 出版时间：May 7, 2010
- 年：2010
- 卷：75
- 期：9
- 页码：3069-3084
- 全文大小：1245K
- 年卷期：v.75,no.9(May 7, 2010)
- ISSN：1520-6904
文摘
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.