Conversion of spinosyn A and spinosyn D to their respective 9- and 17-pseudoaglycones and their aglycones.
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.
Creemer
L C
LC
Elanco Animal Health, Research and Development, Greenfield, Indiana 46140, USA.
Kirst
H A
HA
Paschal
J W
JW
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry*; D006595:Hexosamines / Q000737:chemistry; D018942:Macrolides; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006595:Hexosamines; D018942:Macrolides; C114883:spinosyn A; C114884:spinosyn D; C012325:forosamine