Band 19, Heft 6

Polyoxins and nikkomycins are a class of naturally occurring peptidyl nucleoside antibiotics that show promise as potential antifungal agents due to their potent ability to inhibit chitin synthase, an enzyme responsible for fungal cell wall biosynthesis. Whole cell assays and in vivo studies have shown that these natural products have poor cellular uptake and are metabolically unstable, and there has been a concerted effort to improve their pharmokinetic properties by synthesizing analogs. These have either been designed as natural substrate analogs, transition state mimetics or mechanistic inhibitors. Recent synthetic efforts and the results of their biological studies are briefly described in this review, and the current trends in the design and construction of polyoxin and nikkomycin analogs are discussed.

The synthesis of 1,4-benzoxazine fused heterocycles has been reviewed.

The copper-catalyzed click reaction of organic azides with acetylene gas to give 1,2,3-triazoles using water as solvent was studied. The best yields are obtained in the presence of 10 mol% of CuI and 20 mol% of Et 3 N. Several 1-substituted triazoles were prepared in the yields of 29–96%.

Sequential treatment of 5-bromo-2,4-dichloro-6-(chloromethyl)pyrimidine with 2-aminothiophenol and secondary amines afforded a series of 2-[(5-bromo-2-chloro-6-aminopyrimidin-4-yl)methylthio]aniline derivatives. Reaction of the latter compounds with secondary amines in ethanol gave a family of new 5,7-diamino-5,11-dihydropyrimido[5,4- e ][1,4]benzothiazepines.

A simple and concise one-pot protocol for the synthesis of carboxyl-substituted bisquinoline systems 3a–i is described. The approach involves the Williamson reaction of ethyl 2-(halomethyl)quinoline-3-carboxylates 4a–c with 8-hydroxyquinolines 5a–c followed by hydrolysis.

The reaction of 6-(2-methylpropyl or 2-phenylpropyl)-2-thiouracil-5-carbonitriles ( 4a,b ) with various arylmethyl halides, 2-bromoethyl methyl ether, benzyl chloromethyl ether, and 2-bromomethyl-5-nitrofuran in N,N -dimethylformamide or acetone yielded the corresponding substituted thio-3,4-dihydro-4-oxopyrimidine-5-carbonitrile analogues 5a–h , 6a , b , 7 , and 8a , b , respectively. Treatment of 5c with phosphorus oxychloride and N,N -dimethylaniline yielded the 4-chloropyrimidine derivative 9 , which was allowed to react with various arylthiols, arylamines, and 1-substituted piperazines to yield the respective 4-arylthio 10a–d , 4-arylamino 11a–d , and 4-piperazino 12a,b derivatives. The newly synthesized compounds were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans . Compounds 5e , 5f , 5g , h , 7 , 8a , b , and 12a display marked antibacterial activity, particularly against the Gram-positive bacteria. None of these compounds are active against C. albicans .

Tungstic acid was used as a low-cost and readily available heterogeneous catalyst for the synthesis of 3,3-bis(1 H -indol-3-yl)indolin-2-one derivatives from indoles. The reaction parameters, including catalyst quantity, solvents, temperature, and time were optimized. The present method has several advantages, such as mild conditions, simple work-up, elimination of anhydrous condition, easy recovery of catalyst and its recyclability as compared with existing methods.

Silica-supported boron trifluoride (BF 3 •SiO 2 ) is an efficient, readily available, and reusable catalyst for the synthesis of 2-amino-5-oxo-4-aryl-4 H ,5 H -pyrano[3,2- c ]chromene-3-carbonitrile or carboxylic acid ethyl ester derivatives by condensation of 4-hydroxycoumarin, an aldehyde, and an alkylnitrile.