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

نویسندگان

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

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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عنوان ژورنال:
  • The Journal of organic chemistry

دوره 75 9  شماره 

صفحات  -

تاریخ انتشار 2010