TOTAL SYNTHESIS OF CRYSTALLINE (+ -)-FREDERICAMYCIN-A - USE OF RADICAL SPIROCYCLIZATION/

Crystalline (+/-)-fredericamycin A (1) was synthesized using, as a key step, 5-exo-digonal radical closure of selenide 55. The selenide was generated from the corresponding ketone 54, itself assembled from two components: aldehyde 29 and bromonaphthalene 48. The product of the ra dical cyclization (56) was converted into spiro diketone 59, and the p entadienyl chain was then formed by a Wittig reaction. Selective depro tection of ring A was accompanied by isomerization of the diene system to the required E,E geometry, and treatment with boron tribromide, fo llowed by aqueous hydrolysis in the presence of air, effected selectiv e demethylation and oxidation to (+/-)-1. The radical spirocyclization used in this synthesis is a general method.