基于火蚁毒液生物碱的 2-甲基-6-烷基-Δ-哌啶的合成与抗菌评价。

Synthesis and Antimicrobial Evaluation of Fire Ant Venom Alkaloid Based 2-Methyl-6-alkyl-Δ-piperideines.

机构信息

Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.

National Centers for Natural Products Research, Research Institute of Pharmaceutical Sciences, The University of Mississippi , University, Mississippi 38677, United States.

出版信息

J Nat Prod. 2017 Oct 27;80(10):2795-2798. doi: 10.1021/acs.jnatprod.7b00625. Epub 2017 Oct 12.

DOI:10.1021/acs.jnatprod.7b00625

PMID:29023124

Abstract

The first synthesis of 2-methyl-6-pentadecyl-Δ-piperideine (1), a major alkaloid of the piperideine chemotype in fire ant venoms, and its analogues, 2-methyl-6-tetradecyl-Δ-piperideine (2) and 2-methyl-6-hexadecyl-Δ-piperideine (3), was achieved by a facile synthetic method starting with glutaric acid (4) and urea (5). Compound 1 showed in vitro antifungal activity against Cryptococcus neoformans and Candida albicans with IC values of 6.6 and 12.4 μg/mL, respectively, and antibacterial activity against vancomycin-resistant Enterococcus faecium with an IC value of 19.4 μg/mL, while compounds 2 and 3 were less active against these pathogens. All three compounds strongly inhibited the parasites Leishmania donovani promastigotes and Trypanosoma brucei with IC values in the range of 5.0-6.7 and 2.7-4.0 μg/mL, respectively.

摘要

2-甲基-6-十五烷基-Δ-哌啶（1）的首次合成，这是火蚁毒液哌啶型生物碱的主要生物碱，以及其类似物 2-甲基-6-十四烷基-Δ-哌啶（2）和 2-甲基-6-十六烷基-Δ-哌啶（3），通过从戊二酸（4）和尿素（5）开始的简便合成方法实现。化合物 1 表现出对新型隐球菌和白色念珠菌的体外抗真菌活性，IC 值分别为 6.6 和 12.4μg/mL，对万古霉素耐药粪肠球菌的抗菌活性的 IC 值为 19.4μg/mL，而化合物 2 和 3 对这些病原体的活性较低。所有三种化合物对利什曼原虫前鞭毛体和布氏锥虫的抑制作用均较强，IC 值分别在 5.0-6.7 和 2.7-4.0μg/mL 范围内。