Synthetic studies on dl-aspterric acid, a carotane-type sesquiterpene. II Synthesis of dl-aspterric acid.

Abstract

Total synthesis of dl-aspterric acid (1) has been accomplished. Robinson annulation of the keto ester (2) with methyl vinyl ketone, followed by reduction with LiAlH4 and oxidation with MnO2, afforded the enone alcohol (4), which was converted to the hydroxy-ether (6) via three steps (I2-Ag2O, AgOAc, and alkaline hydrolysis). Successive treatment of 6 with tert-butyldimethylsilyl chloride, tert-BuOK-MeI, NaBH4, Ac2O-pyridine and 5% HCl afforded the hydroxy acetate (18). The hydroxy acetate (18) was converted to the hydroxy ketone (20) via catalytic hydrogenation under medium pressure, Jones oxidation, and alkaline hydrolysis. Treatment of 20 with PCl5 gave the norketone (21), which is the degradation product of 1. The dimethylacetal (25) of 20 was treated with Me3SiCN-SnCl2 to give the methoxy cyanides A (26) and B (27). The major methoxy cyanide B (27) was successively treated with KOH, Me3SiCl-NaI, Ac2O, and 5% HCl to give the monoacetate (31), which was finally converted to 1 via ring contraction with PCl5 and alkaline hydrolysis.