Spinosyn A 17-pseudoaglycone

Forosamine at the 17-position of spinosyns A and D was hydrolyzed under mild acidic conditions to give the corresponding 17-pseudoaglycones. The tri-O-methylrhamnose at the 9-position of the 17-pseudoaglycone of spinosyn A was hydrolyzed under more vigorous acidic conditions to give the aglycone of spinosyn A. However, these conditions led to decomposition of the 17-pseudoaglycone of spinosyn D, presumably due to more facile protonation of the 5,6-double bond to produce a tertiary carbonium ion which undergoes further rearrangements. Spinosyns J and L (3'-O-demethyl spinosyn A and D, respectively) obtained from fermentation of biosynthetically-blocked mutant strains of Saccharopolyspora spinosa, were oxidized to give the corresponding 3'-keto-derivatives and the resultant keto-sugars were then beta-eliminated under basic conditions to give the 9-pseudoaglycones of spinosyns A and D respectively. Forosamine at the 17-position of the 9-pseudoaglycone of spinosyn D was then readily hydrolyzed to yield the aglycone of spinosyn D.

[reaction: see text] Spinosyn G was isolated in the late 1980s as a minor component from the broth of our potent, fermentation-derived insecticide spinosad. Its structure was then tentatively identified as 5' '-epispinosyn A (3) on the basis of (1)H and (13)C NMR data, but the 4' '-epi compound 4 could not be conclusively ruled out with the data available. Described herein are unambiguous syntheses of both 3 and 4, whereby 3 was proved identical to the natural product. Compound 4 was prepared from intact spinosyn A by a novel F-TEDA-promoted oxidative deamination to the 4' '-ketone 5, stereoselective reduction to the equatorial alcohol 6, and nitrogen incorporation via the axial azide 7. Compound 3 was obtained by coupling spinosyn A 17-pseudoaglycone (9) with the N-protected dihydropyran 16 derived from methyl l-ossaminide (14). This gave an approximately 2:1 mixture of anomeric products 17 with the desired equatorial glycoside predominating, which was then converted to 3 by N-deprotection and methylation.