Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of 1 J C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

Md Rokon Ul Karim; Enjuro Harunari; Amit Raj Sharma; Naoya Oku; Kazuaki Akasaka; Daisuke Urabe; Mada Triandala Sibero; Yasuhiro Igarashi

doi:10.3762/bjoc.16.222

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹ J _C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

Beilstein J Org Chem. 2020 Nov 5:16:2719-2727. doi: 10.3762/bjoc.16.222. eCollection 2020.

Authors

Md Rokon Ul Karim¹, Enjuro Harunari¹, Amit Raj Sharma¹, Naoya Oku¹, Kazuaki Akasaka², Daisuke Urabe¹, Mada Triandala Sibero³, Yasuhiro Igarashi¹

Affiliations

¹ Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
² Shokei Gakuin University, 4-10-1 Yurigaoka, Natori, Miyagi 981-1295, Japan.
³ Department of Marine Science, Faculty of Fisheries and Marine Science, Diponegoro University, Semarang, Central Java 50275, Indonesia.

Abstract

Chemical investigation of secondary metabolites from a marine-derived actinomycete strain of the genus Kocuria, isolated from a stony coral Mycedium sp., led to the identification of two new alkanoylimidazoles, nocarimidazoles C (1) and D (2) as well as three known congeners, nocarimidazoles A (3) and B (4) and bulbimidazole A (5). Structure analysis of 1 and 2 by NMR and MS revealed that both are 4-alkanoyl-5-aminoimidazoles with a 6-methyloctanoyl or decanoyl chain, respectively. Two possible positions of the amino group on the imidazole rings (C-2 and C-5) posed a challenge in the structure study, which was settled by the measurement of ¹ J _C,H coupling constants for comparison with those of synthetically prepared model imidazoles. The absolute configurations of the anteisoalkanoyl group present in 1, 4, and 5 were determined by low-temperature HPLC analysis of the degradation products labeled with a chiral anthracene reagent, which revealed that 1 is a mixture of the R- and S-enantiomers with a ratio of 73:27, 4 is the pure (S)-enantiomer, and 5 is the (S)-enantiomer with 98% ee. The present study illustrates the diversity in the stereochemistry of anteiso branching in bacterial metabolites. Compounds 1-4 were moderately antimicrobial against Gram-positive bacteria and fungi, with MIC ranges of 6.25-25 μg/mL.

Keywords: 1JC,H; Kocuria; alkanoylimidazoles; anteiso; nocarimidazole.

Grants and funding

This work was supported by a TPU Young Investigator Overseas Training Expense for E. H. and JSPS KAKENHI Grants JP19K05848 to Y. I., JP18K05827 to N. O., and JP16H06213 to D. U.