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

• Published in: Journal of the American Chemical Society 1998-03, Vol.120 (11), p.2553-2562
• Main Authors: Paquette, Leo A, Collado, Iván, Purdie, Mark
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja974010k

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.