Erciyas E, Erkaleli H I, Cosar G
Ege Universitesi Eczacilik Fakültesi, Bornova-Izmir, Turkey.
J Pharm Sci. 1994 Apr;83(4):545-8. doi: 10.1002/jps.2600830420.
Acyclic alpha,beta-unsaturated ketones were synthesized and treated with either 2-mercaptoethanol or cystenamine hydrochloride under the simulated physiological conditions. The thiol group of these model biological nucleophiles underwent Michael type addition to the activated double bond. The incubation of the bis-Mannich base of 3-benzylidene-2,4-pentanedione with 2-mercaptoethanol, surprisingly, gave rise to the formation of 5-[(2-hydroxyethyl)thio]-1-phenyl-1- penten-3-one (8) in low yield. Evaluation of the compounds versus Gram-positive and Gram-negative bacteria and also a type of fungus indicated that the conjugated ketones and their adducts, except the bis-Mannich base, have antimicrobial activity at 10 micrograms/mL. The Mannich base, 3, showed antibacterial property against only Escherichia coli at 1000 micrograms/mL in spite of containing a bioactive styryl ketone structure and having deamination ability. However, the thiol adducts, which do not contain any alpha,beta-unsaturated ketone function, exhibited similar antimicrobial potency to the conjugated ketone derivatives, possibly due to the exchange reaction with enzymes or coenzymes in the microorganisms.
合成了无环α,β-不饱和酮，并在模拟生理条件下用2-巯基乙醇或盐酸半胱胺进行处理。这些模型生物亲核试剂的硫醇基团对活化的双键进行了迈克尔型加成。令人惊讶的是，3-亚苄基-2,4-戊二酮的双曼尼希碱与2-巯基乙醇孵育，以低产率生成了5-[(2-羟乙基)硫基]-1-苯基-1-戊烯-3-酮(8)。对这些化合物针对革兰氏阳性菌、革兰氏阴性菌以及一种真菌进行评估，结果表明，共轭酮及其加合物（双曼尼希碱除外）在10微克/毫升时具有抗菌活性。曼尼希碱3尽管含有生物活性苯乙烯基酮结构且具有脱氨能力，但仅在1000微克/毫升时对大肠杆菌具有抗菌性能。然而，不含任何α,β-不饱和酮官能团的硫醇加合物表现出与共轭酮衍生物相似的抗菌效力，这可能是由于与微生物中的酶或辅酶发生了交换反应。
