Synthesis of pluraflavin A "aglycone".
The "aglycone" of pluraflavin A (2) has been synthesized. The key features of this synthesis include a 1,3-dipolar cycloaddition between a nitrile oxide (cf. 14) and an olefin (22) to yield an isoxazoline followed by subsequent conversion into the gamma-pyrone of pluraflavin A. The epoxide moiety linked to the pyrone is installed prior to Diels-Alder installation of the D ring, which allows access to a number of potentially active cytotoxic intermediates en route to the final compound. The preliminary in vitro results of two such compounds are also included with the racemic title compound exhibiting cytotoxicity in the nanomolar range.
Wright
Benjamin J D
BJ
Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, New York 10027, USA.
Hartung
John
J
Peng
Feng
F
Van de Water
Ryan
R
Liu
Haibo
H
Tan
Quen-Hui
QH
Chou
Ting-Chao
TC
Danishefsky
Samuel J
SJ
D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry; D006801:Humans
D000880:Anthraquinones; C440630:pluraflavin A; D004317:Doxorubicin