A chemical investigation of strain RD003821, belonging to the underexplored actinomycetes genus Krasilnikovia, led to the discovery of three novel polyketides: two 20-membered glycomacrolides, krasilnikolides A (1) and B (2), and an aglycone of 1, detalosylkrasilnikolide A (3). A major challenge in the structure elucidation of 1 was to determine the anomeric configuration of the α-l-6-deoxytalose (6dTal) unit, which was achieved by J-based configuration analysis (JBCA) that incorporated anomeric carbon- and proton-specific two-bond 13C-1H spin-spin coupling constants as diagnostic parameters. The updated criteria for the conformation/configuration assignment facilitated discrimination of three out of four stereochemical variants at the anomeric and the adjacent C2 positions, which expanded the scope of the JBCA method to determination of the anomeric configuration of aldohexopyranoses. Compounds 1 and 2 are the first macrolides decorated by 6dTal. Compounds 1-3 exhibited cytotoxicity against P388 murine leukemia cells with IC50 values of 14, 8.4, and 3.9 μM, respectively. In addition, 1-3 were antibacterial against the Gram-positive bacterium Kocuria rhizophila with MIC values of 25, 50, and 100 μg/mL. 1 was inhibitory against Staphylococcus aureus with an MIC of 50 μg/mL.
structure elucidation, a-L-6-deoxytalose, glycomacrolide, Krasilnikovia
NCBI PubMed ID: 36482689Publication DOI: 10.1021/acs.jnatprod.2c00781Journal NLM ID: 7906882Publisher: American Society of Pharmacognosy
Correspondence: Y. Igarashi
Institutions: Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan
Methods: 13C NMR, 1H NMR, NMR-2D, IR, extraction, optical rotation measurement, LC-MS, fermentation, antimicrobial assay, conformational analysis, ECD, HPLC-UV, HR-ESI-TOF-MS
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