Hoynamycins A−C, Deoxysugar-Bearing Polyether Polyketides from Marine-Derived Streptomyces hoynatensis 213DD-061, and their Semisynthetic Analogues

Abstract

Hoynamycins A−C (1−3), three new deoxysugar-bearing polyether ionophores, were isolated from the marine-derived actinomycete Streptomyces hoynatensis 213DD-061. Their structures and relative configurations were established by HRESIMS and NMR analyses, single-crystal X-ray diffraction, and PGME analyses. Compounds 1−3 exhibited potent cytotoxicity, while only 1 and 3 showed anti-MRSA activity, indicating distinct structural requirements for the two activities. Semisynthetic modification of 1 revealed pronounced effects of peripheral structural changes on biological activity: the combined deoxysugar cleavage, C-1 methyl esterification, and C-7 O-methylation markedly attenuated both cytotoxic and antimicrobial activities, while C-1 N-phenyl amidation altered the cytotoxicity profile and abolished the antibacterial activity. On the other hand, triphenylphosphonium (TPP) conjugation enhanced cytotoxic potency without conferring appreciable cancer-cell selectivity. Our results expand the structural diversity of glycosylated polyether ionophores and identify peripheral structural elements as determinants of the cytotoxic and antimicrobial activities of the hoynamycin scaffold.