SYNTHETIC STUDIES TOWARD MONO-THF ANNONACEOUS ACETOGENINS - A DIASTEREOSELECTIVE AND CONVERGENT APPROACH TO COROSSOLONE AND (10RS)-COROSSOLINE

This paper describes a diastereoselective approach to the total syntheses of both corossolone (1) and (10RS)-corossoline (2), two naturally occurring cytotoxic annonaceous acetogenins from Annona muricata. 2,3-O-Isopropylidene-D-threitol (3) has be en used as the chiral pool for the preparation of (5R,6R)-5-hydroxy-6-[(tert-butyldimethylsilyl)oxy]-1-octadecene (10). Epoxidation of 10 with m-CPBA and intramolecular ring closure in one pot gave a trans-THF intermediate 11 as the major product. The subsequent reagent-controlled asymmetric propargylation was achieved by treatment of the aldehyde derived from 11 with 2-allenyl-1,3,2-dioxaborolane-(4S,5S)-dicarboxylic acid bis-(1'-methylethyl) ester to afford compound 12 with the threo-trans-threo THF moiety with excellent diastereoselectivity. Epoxide 21 prepared from ethyl L-lactate and undecenoic acid according to our previous methodology was treated with alkynyl anion 13 derived from 12 in the presence of BF3-OEt(2) to give the regioselective ring-opening product 22 with the whole skeleton of the target molecule. Finally, beta-elimination followed by deprotection or by oxidation and then deprotection afforded corossolone and (10RS)-corossoline, whose physical data are coincident with those of the natural products.