New lactimidomycin congeners shed insight into lactimidomycin biosynthesis in Streptomyces amphibiosporus.

Lactimidomycin (LTM, 1) is a macrolide antitumor antibiotic with a glutarimide side chain from Streptomyces amphibiosporus ATCC53964. To further develop LTM and related analogues as drug candidates we have (i) improved LTM production by approximately 20 fold, (ii) identified three new metabolites (2-4) possibly involved in the LTM biosynthetic pathway; (iii) found 3 to be identical with a previously identified isomigrastatin precursor, (iv) determined the absolute stereochemistry of LTM, and (v) produced new LTM rearrangement products 2a-d and 4a-d.