TY - JOUR
T1 - Chemoenzymatic synthesis of amaryllidaceae constituents and biological evaluation of their C-1 analogues. the next generation synthesis of 7-deoxypancratistatin and trans -dihydrolycoricidine
AU - Collins, Jonathan
AU - Rinner, Uwe
AU - Moser, Michael
AU - Hudlicky, Tomas
AU - Ghiviriga, Ion
AU - Romero, Anntherese E.
AU - Kornienko, Alexander
AU - Ma, Dennis
AU - Griffin, Carly
AU - Pandey, Siyaram
PY - 2010/5/7
Y1 - 2010/5/7
N2 - 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.
AB - 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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U2 - 10.1021/jo1003136
DO - 10.1021/jo1003136
M3 - Article
C2 - 20373760
AN - SCOPUS:77951783308
SN - 0022-3263
VL - 75
SP - 3069
EP - 3084
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 9
ER -