Total Synthesis of Spinosyn A. 2. Degradation Studies Involving the Pure Factor and Its Complete Reconstitution

A total synthesis of natural levorotatory spinosyn A ( 1 ) has been achieved. The first objective, to confirm the absolute configurational assignment of tricyclic ketone 2 prepared earlier, was accomplished by oxidative degradation of the macrocyclic lactone ring in 1 . The route began with the implementation of a four-step one-pot process that resulted in the efficient conversion of 6 into 18 . A combination of periodate cleavage and peracid oxidation events then led to 2 . In the reconstruction phase, a Pd-catalyzed coupling of a vinylstannane with an acid chloride reestablished the great majority of the structure in an enantiocontrolled manner. Once macrolactonization had been effected, the 2,3,4-tri- O -methylrhamnose unit was introduced first with exceptionally good stereocontrol. The final glycosidation, which involved a 2-mercaptopyrimidine derivative of d -forosamine, was met with an expectedly diminished percentage of the desired β-anomer.