Antimycotic 2-alkyldithio, 2-aralkyldithio, 2-aryldithiobenzamides

Some 2-alkyldithio, 2-aralkyldithio, 2-aryldithio benzoic acids, their methyl esters and N-monosubstituted amides were prepared and tested in vitro against Candida albicans and Trichophyton mentagrophytes. Some N-monosubstituted amides displayed activities similar to those of clotrimazole and pyrrolnitrin. Against Candida albicans, N-monosubstituted amides exhibited a generally higher activity than the corresponding N-monosubstituted amides of 2,2'-dicarboxydiphenyldisulfide.     

2'-Deoxy-2'-methylenecytidine and 2'-deoxy-2',2'-difluorocytidine 5'-diphosphates: potent mechanism-based inhibitors of ribonucleotide reductase

It has been found that 2'-deoxy-2'-methyleneuridine (MdUrd), 2'-deoxy-2'-methylenecytidine (MdCyd), and 2'-deoxy-2',2'-difluorocytidine (dFdCyd) 5'-diphosphates (MdUDP (1) MdCDP (2) and dFdCDP (3), respectively) function as irreversible inactivators of the Escherichia coli ribonucleoside diphosphate reductase (RDPR). 2 is a much more potent inhibitor than its uridine analogue 1. It is proposed that 2 undergoes abstraction of H3' to give an allylic radical that captures a hydrogen atom and decomposes to an active alkylating furanone species. RDPR also accepts 3 as an alternative substrate analogue and presumably executes an initial abstraction of H3' to initiate formation of a suicide species. Both 2 and 3 give inactivation results that differ from those of previously studied inhibitors. The potent anticancer activities of MdCyd and dFdCyd indicate a significant chemotherapeutic potential. The analogous RDPR of mammalian cells should be regarded as a likely target and/or activating enzyme for these novel mechanism-based inactivators.     

2-苯基-1-丁醇与2-二甲氨基-2-苯基丁腈的合成

目的为马来酸曲美布汀的重要中间体2-二甲氨基-2-苯基-1-丁醇的合成奠定基础。方法苯乙腈与溴乙烷进行烃化反应得2-苯基-1-丁腈,所得产物经水解得2-苯基-1-丁酸,然后通过硼氢化钠-碘体系还原得2-苯基-1-丁醇;苯乙腈与N-溴代丁二酰亚胺进行卤代反应得溴代苯乙腈,所得产物与二甲胺进行烃化反应得2-二甲氨基苯乙腈,然后与溴乙烷进行烃化反应得2-二甲氨基-2-苯基丁腈。结果合成了2-苯基-1-丁醇和2-二甲氨基-2-苯基丁腈,总收率为分别为51%和59.4%。目标产物的结构经核磁共振氢谱、质谱确证。结论本合成方法原料易得,操作简单,收率较高,适合于工业化生产。     

3S-(2R-2-苯基-2-环戊基-2-羟基乙氧基)奎宁环烷的晶体结构

选择性抗胆碱药3-(2-苯基-2-环戊基-2-羟基乙氧基)奎宁环烷盐酸盐的分子结构中有两个手性碳原子,其中奎宁环3位的手性碳绝对构型已知。本文报道用X衍射技术,测定了其中一个光学异构体(S-1)的碘甲烷季铵盐的分子结构,确定了另外一个手性碳的绝对构型。该化合物命名为:S-(2R-2-苯基-2-环戈基-2-羟基-乙氧基)-奎宁环烷。     

Synthesis and biological activities of 2-pyrimidinone nucleosides. 2. 5-Halo-2-pyrimidinone 2'-deoxyribonucleosides

1-(2-Deoxy-beta-D-ribofuranosyl)-5-bromo-2-pyrimidinone (BrPdR) and 1-(2-deoxy-beta-D-ribofuranosyl)-5-iodo-2-pyrimidinone (IPdR) have been synthesized by condensation of the appropriate silylated bases 2a and 2b, respectively, with 3,5-bis-O-(p-chlorobenzoyl)-2-deoxy-alpha-D-ribofuranosyl chloride (8) in 1,2-dichloroethane, in the presence of SnCl4, followed by separation of the anomeric blocked nucleosides via column chromatography and subsequent deprotection with methanolic ammonia. Both BrPdR and IPdR exhibited significant antiherpes activities against various strains of HSV-1 and HSV-2, the latter compound (IPdR) showing the higher activity as well as the stronger binding to the virus-specific thymidine kinase.     

2-吡啶甲醇及2-吡啶甲醛的合成

以 2 -甲基吡啶为原料、过氧化氢为氧化剂制备 2 -吡啶甲醇和 2 -吡啶甲醛,工艺方法经济、安全     

Penicillin-enhanced chemiluminescence of the luminol-H2O2-Co2+ system.

The luminol-H2O2-Co2+ system has been widely used in chemical and biological analysis. We report here an investigation of the observation that penicillins have the ability to prolong and enhance the intensity of chemiluminescence from luminol. The basis of this phenomenon appears, as revealed by difference spectroscopy, to be the formation of a complex between the beta-lactam and the superoxide ion. The latter is the oxidizing species responsible for the oxidation of luminol in alkaline solution and has a mean lifetime, in solution, of milliseconds. The stabilization of the superoxide ion by penicillin complexation extends the effective lifetime of the superoxide ion by a few orders of magnitude and thereby allows for more efficient oxidation of the beta-lactam. Several penicillins were determined by their enhancement of luminol chemiluminescence. A detection limit of 100 ng mL was obtained for penicillin G with a less-than-ideal detection system.