504-99-4Relevant articles and documents
An Efficient Synthesis of Natural Tribolure
Shi, Jianmin,Liu, Lu,Tang, Meng,Zhang, Tao,Bai, Hongjin,Du, Zhenting
, p. 197 - 201 (2020)
An efficient synthesis of natural tribolure has been achieved through an asymmetric methylation as a key step. Natural tribolure is a mixture of four stereoisomers, so racemic 2-methylbutan-1-ol was used as starting material. After a C5+C4 strategy and then a mixed Evan’s template inductive methylation, the key intermediate was obtained. Finally, the natural product tribolure (4:4:1:1 of stereoisomers, respectively) was obtained in 10 linear steps and in 34.2% overall yield.
Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: Application of 1JC,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites
Akasaka, Kazuaki,Harunari, Enjuro,Igarashi, Yasuhiro,Karim, Rokon Ul,Oku, Naoya,Sharma, Amit Raj,Sibero, Mada Triandala,Urabe, Daisuke
, p. 2719 - 2727 (2020/12/01)
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 1JC,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.
Synthesis and Bioactivity Investigation of the Individual Components of Cyclic Lipopeptide Antibiotics
Cui, A-Long,Hu, Xin-Xin,Gao, Yan,Jin, Jie,Yi, Hong,Wang, Xiu-Kun,Nie, Tong-Ying,Chen, Yang,He, Qi-Yang,Guo, Hui-Fang,Jiang, Jian-Dong,You, Xue-Fu,Li, Zhuo-Rong
, p. 1845 - 1857 (2018/03/21)
In this paper, 26 natural polymyxin components and a new derivative S2 were synthesized, and their differences in efficacy and toxicity have been investigated. Almost all of the synthesized components showed strong activity against both susceptible and resistant strains of E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii. The toxicities were obviously different between the components. Only some of the components were tested for toxicity in vivo. Compounds E2, E2-Val, A2, M2, D2, and S2 showed obviously lower renal cytotoxicity and acute toxicity than polymyxins B and E. The in vivo nephrotoxicity of E2, M2, and S2 was similar to that of polymyxin E. Compound S2, with four positive charges, was especially interesting as it possessed both increased efficacy and decreased toxicity. The SAR and toxicity studies indicated that further structural modification could concentrate on polymyxin S. The results also indicated that S2 could be a new drug candidate.
