Study of alkaline hydrolysis of anilides of benzylpenicillin

To examine the stability of penicillin and its derivatives in an alkaline medium the hydrolysis of substituted anilides of benzylpenicillin was studied at pH 9.1 and temperatures of 25, 30, and 40°. The velocity constants of the reaction and the activation energy of the process were calculated; hydrolysis of the amide bond of the-lactam ring of anilides of benzylpenicillin under these conditions was shown to be a pseudomonomolecular reaction. A satisfactory correlation was found between the logarithms of the velocity constants of the reaction and the pK of the amine. Hammett's equation is applicable to this process. The low absolute values of=0.33 indicate that the reaction is only slightly sensitive to structural changes in the anilide molecule.Translated from Khimiko-Farmatsevticheskii Zhurnal, No. 2, pp. 17–21, February, 1967.     

Further studies on the catalysis of hydrolysis and aminolysis of benzylpenicillin by metal chelates

It was suggested previously that the very rapid catalysis of benzylpenicillin hydrolysis and aminolysis by zinc ion and tris(hydroxymethyl)aminomethane (tromethamine) was mediated by a ternary complex in which the metal ion not only held the substrate and tromethamine in close proximity but also lowered the pKa of a bound tromethamine hydroxyl group making it a very powerful nucleophile. In this study the scope of this reaction was explored further by examining the effects of changes in substrate side chain, metal ion, and amino alcohols. All of the penicillins studied showed about the same rate of reaction. Of the other metal ions examined Cu2+ and Ni2+ showed no activity, Mn2+ very slight activity, and Cd2+ and Co2+ somewhat greater activity. The latter was the most effective of this group but was 40 times slower than zinc. The results with a number of amino alcohols provided additional evidence for the ternary complex mechanism. Studies with the methyl ester of benzylpenicillin indicated that the metal ion is bound to the antibiotic at the carboxylate site and that a different mechanism is involved in the slower catalysis observed with the ester. Some comparison is made with a zinc-dependent beta-lactamase.     

汞量电位法测定青霉素钾、钠含量时水解时间的探讨

目的对应用汞量电位法测定PG-K、Na含量时碱水解所需的时间进行研究.方法采用RP-HPLC法和TLC法分别对碱水解0～15分钟的溶液进行测定.结果PG-K2分钟即可完全水解.对3批青霉素钾和5批青霉素钠的测定与中国药典(Chp1995)水解15分钟的方法比较,结果一致.结论采用汞量法测定PG-K、Na含量时,碱水解时间可修订为5分钟,以提高检验速度.     

Acid catalyzed hydrolysis of a series of zopiclone analogues

The pKa values of acid-base equilibria involved in the protonation of zopiclone and analogues are determined by UV-visible absorption spectrometry and pH-metry. Hydrogen ion catalysis is evidenced in the carbamate hydrolysis.     

苄青霉素亚砜对-甲氧基苄酯的合成研究

以苄青霉素钾盐为原料，用低浓度CH3CO3H作氧化剂．所得苄青霉素亚砜以固体形式直接从溶液中结晶析出，再以对-甲氧基苄氯酯化，制得头孢类药物的母核7-苯乙酰胺基-3-氯甲基头孢烷酸对甲氧苄酯（GCLE）的关键中间体苄青霉素亚砜对-甲氧基苄酯，实验总收率82．6％。本工艺只使用一种有机溶剂，缩短了皮应时间，降低了成本，适合规模生产。     

普鲁卡因青霉素治疗早期梅毒的疗效

目的分析普鲁卡因青霉素治疗早期梅毒的疗效。方法回顾分析我科应用普鲁卡因青霉素(80万U/d,肌肉注射,1次/d,连续15d)治疗26例早期梅毒患者的临床及血清学疗效。结果普鲁卡因青霉素治疗后1个月,24例显性梅毒患者均临床治愈。2年随访结束时,88.46%的患者达到血清学治愈(23/26);11.54%的患者为血清学固定(3/26)。一期梅毒TRUST滴度在治疗后3个月内下降最显著(P<0.01);二期梅毒TRUST滴度在治疗后9个月内明显下降(P<0.05),其中以治疗后6个月内下降最显著(P<0.01)。结论普鲁卡因青霉素治疗早期梅毒有效。     

Antibacterially active substituted anilides of carboxylic and sulfonic acids

Anilides of carboxylic and sulfonic acids were prepared and tested for antimicrobial activity. While these anilides were ineffective against Gram-negative organisms, there was a good correlation between chemical structure and biological activity against Gram-positive species. Both the nature and position of the benzene ring substituents and the length of the carbon side chain affected the activity and specificity of the compounds. The highest activity was observed when the acyl or sulfuryl moiety had a C7-C9 side chain attached. The CONH and SO2NH bridging groups were equally effective. The attachment of COOH or COOCH3 groups in the omega-position did not effect activity, but the substitution of the acidic proton of the sulfonamide group by an alkyl group rendered the compound inactive. Six compounds, which were substituted anilides of sulfonic acids, fatty acids, or the analagous alpha-methylene-substituted acids, were bacteriostatic at 10 ppm against Bacillus cereus, Staphylococcus aureus, Streptococcus faecalis, and Lactobacillus plantarum. One of these compounds, 2-hydroxy-5-nitroanilide of alpha-methylenedecanoic acid, was bactericidal at 1 ppm.