All eight possible mono-beta-D-glucosides of validoxylamine A. I. Preparation and structure determination

Validamycin A is the major and most active compound among the validamycin complex. Since the site of beta-glucosidic attachment to validoxylamine A (1) was expected to affect the activity against the pathogenic fungus, Rhizoctonia solani, all eight possible mono-beta-D-glucosides of 1 were prepared. 2-O-, 4-O-, 4'-O-, and 7'-O-beta-D-glucopyranosylvalidoxylamine A (2, 4, 6 and 9, respectively) were prepared by microbial beta-glycosylation of 1 with strains of Rhodotorula sp. 7-O- and 6'-O-beta-D-glucopyranosylvalidoxylamine A (5a and 8a, respectively) were prepared semisynthetically through microbial formation of 7-O-beta-D-glucopyranosylvalidamine (10), oxidation of the primary amine of 10 to a ketone, and coupling of the ketone derivative with valienamine, and through microbial formation of 6-O-beta-D-glucopyranosylvalienamine (11), and coupling of 11 with (2R)-(2,4/3,5)-2,3,4-trihydroxy-5-hydroxymethylcyclohexanone (12), respectively. 3-O- and 5'-O-beta-D-glucopyranosylvalidoxylamine A (3a and 7a, respectively) were chemically synthesized.