Synthetic studies on C-aryl glycoside natural products: The papulacandins and aquayamycin

The synthesis of the papulacandin and chaetiacandin C-aryl glycoside nuclei is described. The papulacandins and chaetiacandin are antifungal antibiotics and are ideal candidates for illustrating our “reverse polarity” strategy for the synthesis of C-aryl glycosides of the Group I substitution pattern. In this methodology, 1,2-addition of a protected nucleophilic glycal to a suitably protected electrophilic quinone followed by reductive aromatization of the resulting quinol, affords phenols that bear glycals in the para position. Epoxidation and spiroketalization of this C-aryl glycoside intermediate affords the papulacandin nucleus. Hydroboration of the C-aryl glycoside intermediate delivers the chaetiacandin nucleus.; The synthesis of the C-aryl diglycoside of the papulacandins and chaetiacandin was next studied. Our methodology of adding lithiated glycals to quinones was extended to the use of the disaccharide D-lactal. Lithiation studies were conducted using a hexasilylated derivative of D-lactal and then the successfully lithiated lactal was used in 1,2-additions to quinones. The lithiated lactal was also transmetalated to the stannyl lactal and then used in a Stille-type coupling reaction with an aryl bromide. Studies directed toward the synthesis of the chiral tetraunsaturated side chain of Papulacandin D are also detailed.; Finally, the structure of the antitumor antibiotic, aquayamycin, was studied. Model compounds were synthesized by employing 1,2-additions of alkyl and aryl lithiums to functionalized quinones.