Atypical Angucyclinones with Ring Expansion and Cleavage from a Marine Streptomyces sp.

A unique ring C-expanded angucyclinone, oxemycin A ( 1 ), and seven new ring-cleavage derivatives ( 2 - 5 and 9 - 11 ) were isolated from the marine actinomycete Streptomyces pratensis KCB-132, together with eight known analogues ( 6 - 8 and 12 - 16 ). Their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffractions, and NMR and ECD calculations. Among these atypical angucyclinones, compound 1 represented the first seven-membered ketoester in the angucyclinone family, which sheds light on the origin of fragmented angucyclinones with C-ring cleavage at C-12/C-12a in the Baeyer-Villiger hypothesis, such as 2 - 4 , while the related "nonoxidized" analogues 5 - 8 seem to originate from a diverse pathway within the Grob fragmentation hypothesis. Additionally, we have succeeded in the challenging separation of elmenols E and F ( 12 ) into their four stereoisomers, which remained stable in aprotic solvents but rapidly racemized under protic conditions. Furthermore, the absolute configurations of LS1924 and its isomers ( 14 and 15 ) were assigned by ECD calculations for the first time. Surprisingly, these two bicyclic acetals are susceptible to hydrolysis in solution, resulting in fragmented derivatives 17 and 18 with C-ring cleavage between C-6a and C-7. Compared with ring C-modified angucyclinones, ring A-cleaved 11 was more active to multiple resistant "ESKAPE" pathogens with MIC values ranging from 4.7 to 37.5 μg/mL.