Gershon H, Shanks L
J Med Chem. 1977 Apr;20(4):606-9. doi: 10.1021/jm00214a038.
Twelve esters (C1-C6) of erythro- and threo-2-bromo-3-fluorosuccinic acid and related compounds were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes at pH 5.7 and 7.0 in the absence and presence of 10% beef serum in Sabouraud dextrose agar. At pH 7.0 in the presence of 10% beef serum, no consistent pattern in the fungitoxicity of the erythro- and threo-2-bromo-3-fluorosuccinate esters was seen. Increasing the length of the ester function affects fungitoxicity as follows: C2 greater than C1 greater than C3 greater than C4 greater than C5 greater than C6. The most fungitoxic compound in this study was threo-ethyl 2-bromo-3-fluorosuccinate (C. albicans, 14 mug/ml; A. niger, 30 mug/ml; M. mucedo, 9 mug/ml; T. mentagrophytes, 5 mug/ml). Due to the ease of dehydrohalogenation, the fungitoxicity of 2-bromo-3-fluorosuccinic acid esters may be the result of a mixture composed of the parent compound, the bromo- and fluorofumaric acid esters, and HF and HBr of which part may be formed extracellularly and part within the cell.
在pH值为5.7和7.0的条件下，于不含和含有10%牛血清的沙氏葡萄糖琼脂中，对12种赤式和苏式-2-溴-3-氟琥珀酸酯及其相关化合物针对白色念珠菌、黑曲霉、毛霉和须癣毛癣菌的抗真菌活性进行了测试。在pH值为7.0且含有10%牛血清的情况下，未观察到赤式和苏式-2-溴-3-氟琥珀酸酯的杀真菌毒性存在一致规律。酯官能团长度的增加对杀真菌毒性的影响如下：C2＞C1＞C3＞C4＞C5＞C6。本研究中杀真菌毒性最强的化合物是苏式-2-溴-3-氟琥珀酸乙酯（白色念珠菌，14微克/毫升；黑曲霉，30微克/毫升；毛霉，9微克/毫升；须癣毛癣菌，5微克/毫升）。由于易于脱卤化氢，2-溴-3-氟琥珀酸酯的杀真菌毒性可能是由母体化合物、溴代和氟代富马酸酯以及HF和HBr组成的混合物的结果，其中部分可能在细胞外形成，部分在细胞内形成。
