Acyclic congeners from Actinoalloteichus cyanogriseus provide insights into cyclic bipyridine glycoside formation.

Inactivation of the O-methyltransferase gene crmM of Actinoalloteichus cyanogriseus WH1-2216-6 led to a mutant that produced three new acyclic bipyridine glycosides, cyanogrisides E-G (1-3). Further chemical analysis of the wild strain yielded 1 and another new analogue, cyanogriside H (4). Compounds 1-4 possess a skeleton consisting of a 2,2'-bipyridine and a d-quinovose or l-rhamnose sugar moiety. Cyanogriside G (3) was considered to be a key biosynthetic intermediate of the cyclic bipyridine glycosides cyanogrisides A-D. Compounds 2 and 3 showed cytotoxicities against HCT116 and HL-60 cells, and compounds 1 and 4 were cytotoxic on K562 cells.