10.1007/s00044-011-9689-y
The research focuses on the synthesis and evaluation of new compounds derived from metronidazole and amino acids and their esters as potential antiparasitic agents. The synthesis involved a reaction between 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetic acid and various amino acid esters in the presence of N,N'-carbonyldiimidazole (CDI) and triethylamine (TEA), followed by hydrolysis with sodium hydroxide and acidification with hydrochloric acid to obtain the corresponding acids. The synthesized compounds were characterized using elemental analysis and spectroscopic techniques such as 1H-NMR, 13C-NMR, and mass spectrometry. The biological activity of these compounds was assessed through in vitro antiamoebic and antigiardial activity assays, as well as cytotoxicity tests on Hep-2 and Vero cell lines, with metronidazole serving as a standard drug for comparison. The study aimed to identify new derivatives with enhanced antiparasitic activity and lower cytotoxicity, which could contribute to overcoming drug resistance in pathogens.
10.1021/jo00392a018
The research focuses on the development of a new strategy for the regiospecific imidazole alkylation of protected histidines, with the aim of synthesizing modified versions of the natural amino acid that could potentially be used as enzyme inhibitors or hormone antagonists. The study introduces a phenacyl group as a protecting group for the distal imidazole nitrogen atom, allowing for the efficient alkylation at the N(3) position of N-BOC-1-phenacyl-L-histidine methyl ester. The subsequent reductive removal of the phenacyl group from N(1) of the resulting imidazolium intermediate with zinc and acetic acid provides a flexible route to 3-substituted L-histidines. The research successfully demonstrates the synthesis of various 3-substituted histidines using this method, which is particularly useful for introducing secondary benzylic alkyl groups and electron-rich benzyl substituents. Chemicals used in the process include L-histidine methyl ester, N,N-carbonyldiimidazole, phenacyl bromide, alkyl and aryl halides, zinc, acetic acid, and various solvents such as chloroform, dichloromethane, acetonitrile, and tetrahydrofuran.
10.1016/S0040-4039(01)91879-9
The study details the synthesis of 5-acetoxy-9-oxotridecanolactone as a model for erythronolide B, the aglycone of erythromycin B. The researchers aimed to develop a route to 5-acetoxy-13-hydroxy-9-oxotridecanoic acid, with the intention of lactonization at the final stage of macrolide synthesis. The synthesis involved assembling a thirteen-carbon backbone from two cyclopentanoid and one propanoid unit. Key steps included alkylation of the potassio salt of cyclopentanone carboxylic ester with 1,3-dibromopropane, decarboxylation with HBr, Baeyer-Villiger oxidation using CF3CO3H, and further alkylation and decarboxylation steps. The study also involved protecting and unmasking the cyclopentanone carbonyl group, reduction of an ester group with LiAlH4, and oxidation with Collins' reagent. The final lactonization was achieved using p-toluenesulfonyl chloride and Et3N, or alternatively, 1,1'-carbonyldiimidazole and sodium t-amylate. The synthetic route demonstrated potential applicability to erythronolide and other macrolide systems.
10.1021/jm00388a017
The research investigates the synthesis and antitumor activity of substituted phenazine-1-carboxamides as potential antitumor agents. The study aims to explore the structure-activity relationships (SAR) of these compounds and identify derivatives with enhanced antitumor properties. The researchers synthesized a series of N-[2-(dimethylamino)ethyl]phenazine-1-carboxamides with various substituents (such as methyl, methoxy, and chloro groups) at different positions on the phenazine ring. Key chemicals used in the synthesis include phenazine-1-carboxylic acids, N-[2-(dimethylamino)ethyl]amine, and coupling agents like 1,1'-carbonyldiimidazole or thionyl chloride. The study found that the cytotoxicity of the phenazine-1-carboxamides correlates positively with the electron-withdrawing power of the substituent groups, with 9-substituted compounds showing the most activity. The most active compound identified was the 9-methoxy derivative, which demonstrated significant antitumor activity against Lewis lung carcinoma in mice, comparable to the best DNA-intercalating agents described to date. The research concludes that the phenazine-1-carboxamide series holds promise for further development as antitumor drugs, with clear guidelines provided for future work based on the observed SAR.
10.1021/op400113a
The study details an enhanced method for synthesizing trimethobenzamide hydrochloride (Ia), an antiemetic agent used to treat nausea. The researchers aimed to develop a process that avoids common impurities formed during the coupling of 4-(2-dimethylaminoethoxy)benzyl amine (IV) with 3,4,5-trimethoxy benzoic acid (V). They experimented with various coupling reagents and found that N,N'-carbonyldiimidazole (CDI) provided the best results. By optimizing the mole equivalents of CDI, they achieved a high-purity product without the need for column chromatography or repeated crystallization. The final process involved reacting 3,4,5-trimethoxy benzoic acid with CDI to form an intermediate, which was then coupled with 4-(2-dimethylaminoethoxy)benzyl amine in the presence of potassium carbonate, yielding trimethobenzamide hydrochloride with a purity of =99.5% and a satisfactory yield.
C,
Xi
