（±）-2-甲氧基十四烷酸的全合成及其体外抗真菌活性

Total synthesis and in vitro-antifungal activity of (+/-)-2-methoxytetradecanoic Acid.

作者信息

Carballeira Néstor M, Ortiz Denisse, Parang Keykavous, Sardari Soroush

机构信息

Department of Chemistry, University of Puerto Rico, San Juan, Puerto Rico.

出版信息

Arch Pharm (Weinheim). 2004 Mar;337(3):152-5. doi: 10.1002/ardp.200300824.

DOI:10.1002/ardp.200300824

PMID:15038060

Abstract

The marine fatty acid (+/-)-2-methoxytetradecanoic acid was synthesized in two steps (71% overall yield) starting from commercially available methyl-2-hydroxy-tetradecanoate. The title compound was antifungal against Candida albicans (ATCC 14053) in RPMI medium and Aspergillus niger (ATCC 16404) and Cryptococcus neoformans (ATCC 66031) in SDB medium at the minimum inhibitory concentration (MIC) of 100 mM, which compares to the fungitoxicity of a 2-iodotetradecanoic acid against the same fungi. The title compound was also five to ten times more cytotoxic than capric acid to C. albicans and A. niger in the tested medium but comparable in cytotoxicity to either capric acid and its 2-methoxylated analog to C. neoformans. The antifungal activity of (+/-)-2-methoxytetradecanoic acid is explained in terms of inhibition of N-myristoyltransferase.

摘要

海洋脂肪酸（±）-2-甲氧基十四烷酸以市售的2-羟基十四烷酸甲酯为起始原料，分两步合成（总产率71%）。该标题化合物在RPMI培养基中对白色念珠菌（ATCC 14053）具有抗真菌活性，在SDB培养基中对黑曲霉（ATCC 16404）和新型隐球菌（ATCC 66031）具有抗真菌活性，最低抑菌浓度（MIC）为100 mM，这与2-碘十四烷酸对相同真菌的杀真菌毒性相当。在测试培养基中，该标题化合物对白色念珠菌和黑曲霉的细胞毒性也比癸酸高五到十倍，但对新型隐球菌的细胞毒性与癸酸及其2-甲氧基化类似物相当。（±）-2-甲氧基十四烷酸的抗真菌活性是通过抑制N-肉豆蔻酰转移酶来解释的。