Amicoumacin C

Herein, we report a concise and stereoselective approach for the asymmetric total synthesis of hetiamacins A-F on the basis of the total synthesis of amicoumacin C, which could be synthesized from a known l-aspartic acid derivative. The synthesis of hetiamacin A was accomplished by an 11-step sequence that featured 1,3-oxazinane ring formation of amicoumacin B followed by amidation in one pot. Hetiamacins B-F were synthesized from amicoumacin A in only one step.

Enantioselective total syntheses of 12 amicoumacin-type natural products are accomplished with a palladium(II)-catalyzed C-H alkylation as the key step to furnish the 3,4-dihydroisocoumarin scaffold. The target chemicals are assembled in a convergent protocol by merging 3,4-dihydroisocoumarin derived amine part with categories of acid segments that are efficiently prepared by chemoselective catalytic oxidation of chiral 1,2-dihydroxyethylfuran-2(5H)-ones. Afterward, the cytotoxicity of amicoumacins on five cancer cell lines and one normal cell line is investigated.

The rise in antibiotic-resistant bacterial strains prompting nosocomial infections drives the search for new bioactive substances of promising antibacterial properties. The surfaces of seaweeds are rich in heterotrophic bacteria with prospective antimicrobial substances. This study aimed to isolate antibacterial leads from a seaweed-associated bacterium. Heterotrophic Bacillus amyloliquefaciens MTCC 12716 associated with the seaweed Hypnea valentiae, was isolated and screened for antimicrobial properties against drug-resistant pathogens. The bacterial crude extract was purified and three novel amicoumacin-class of isocoumarin analogues, 11'-butyl acetate amicoumacin C (amylomacin A), 4'-hydroxy-11'-methoxyethyl carboxylate amicoumacin C (amylomacin B) and 11'-butyl amicoumacin C (amylomacin C) were isolated to homogeneity. The studied amylomacins possessed potential activities against Pseudomonas aeruginosa, vancomycin-resistant Enterococcus faecalis, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and Shigella flexneri with a range of minimum inhibitory concentration values from 0.78 to 3.12 µg/mL, although standard antibiotics ampicillin and chloramphenicol were active at 6.25-25 µg/mL. Noticeably, the amylomacin compound encompassing 4'-hydroxy-11'-methoxyethyl carboxylate amicoumacin C functionality (amylomacin B), displayed considerably greater antagonistic activities against methicillin-resistant S. aureus, vancomycin-resistant E. faecalis, Vibrio parahaemolyticus, Escherichia coli, and K. pneumoniae (minimum inhibitory concentration 0.78 μg/mL) compared to the positive controls and other amylomacin analogues. Antimicrobial properties of the amylomacins, coupled with the presence of polyketide synthase-I/non-ribosomal peptide synthetase hybrid gene attributed the bacterium as a promising source of antimicrobial compounds with pharmaceutical and biotechnological applications.