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

Abstract

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.

Unravelling key enzymatic steps in C-ring cleavage during angucycline biosynthesis

“…Either mechanism requires several reduction steps for their completion, particularly at C7, which warrants the future study of the reductases encoded in the lug cluster. Importantly, epoxidation is an essential prior step to both pathways, and not an alternative route to BVO as generally believed 25 , 55 .…”

Ethylidene-Tethered Chromene–Pyrone Hybrids as Potential Plant-Growth Regulators from an Endolichenic Phaeosphaeria Species

“…The major factor affecting the ECD spectrum of 2 is the hindered rotamerism around the C-6/C-5′ bond, which dictates the reciprocal arrangement between the two chromophoric moieties, while the impact of the C-8/C-8′ stereogenic centers is minor. This is a similar situation to some bis-chromophoric compounds displaying multiple stereogenic elements, 30,31 where only one of them affects the ECD spectrum. To reduce the number of conformers and then the computational cost, the ethyl groups were replaced by methyl ones, so a model (2-trunc) with a single stereogenic center had to be considered.…”

Asp-containing actinomycin and tetracyclic chromophoric analogues from the Streptomyces sp. strain S22

“…In this study, multiple resistant “ESKAPE” pathogens were selected to test the antibacterial activity of actinomycins 1–3 , using ampicillin, amikacin, and ciprofloxacin as positive controls (Table 2). 17 1–3 were active towards all tested strains with MIC values ranging from 1.25 to 80.0 μg mL −1 . In addition, the HepG2 liver carcinoma cell line was chosen to assess the cytotoxicities of the isolated actinomycins, using actinomycin D as the positive control.…”