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| Chemical and physical data | |
| Formula | C9H10O3 |
| Molar mass | 166.176 g·mol−1 |
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Premethylenomycin C lactone is anatural product with potentantibiotic activity, effective against drug-resistant bacteria such asmethicillin-resistantStaphylococcus aureus (MRSA) andvancomycin-resistantEnterococcus (VRE).[1][2]
The compound was identified unintentionally during investigations of the methylenomycin biosyntheticgene cluster inStreptomyces coelicolor, a bacterium found in soil.[1] Genetic blockade of a specific enzymatic step by deletion of the mmyE gene led to the accumulation and isolation of previously uncharacterized intermediates, including pre-methylenomycin C and itslactone derivative.[2][3]
In thebiosynthetic pathway that producesmethylenomycin A, premethylenomycin C lactone is an early intermediate.Hydrolysis of the lactone ring followed bydehydration yields methylenomycin C, which is subsequentlyoxidized to form theepoxide methylenomycin A.[2]
Compared with methylenomycin A and methylenomycin C, premethylenomycin C and its lactone precursor exhibit antimicrobial activity that is one to twoorders of magnitude greater against a range ofGram-positive bacteria, including antibiotic-resistant isolates ofStaphylococcus aureus andEnterococcus faecium.[2] It also does not have theα-methylene-γ-butyrolactonepharmacophore of methylenomycin A and methylenomycin C, meaning it has a differentmode of action.[2] These properties highlight the compounds in this metabolic series as potential leads for developing new antibiotics to combatantimicrobial resistance.[2]
Beyond its natural production, premethylenomycin C lactone can be prepared synthetically via adiastereoselective phosphine-mediated (3 + 2) cycloaddition reaction, providing a route for larger‑scale preparation andstructure–activity relationship studies.[4]