Dean S. Wise

The synthesis and chemistry of certain anthelmintic benzimidazoles.

A basis for interest in the benzimidazole ring system as a nucleus from which to develop potential chemotherapeutic agents was established in the 1950s when it was found that 5,6-dimethyl-l-(alpha-D-ribofuranosyl)benzimidazole (I) was an integral part of the [structure: see text] structure of vitamin B(12). As a result of these interests and extensive studies, one health related arena that has benefited greatly has been the treatment of parasitic diseases. The discovery of thiabendazole in 1961 further spurred chemists around the world to design and synthesize several thousand benzimidazoles for screening for anthelmintic activity but less than twenty of them have reached commercial use. Much of this work has been done by pharmaceutical companies and is only reported in the patent literature. In this paper, Leroy Townsend and Dean Wise review the development of some of the synthetic methods that have been critical to the preparation of the benzimidazoles of anthelmintic importance. Only a few molecules that demonstrate the processes are discussed here, but numerous reviews of the synthesis and chemistry of other benzimidazoles are available.

An efficient and stereospecific synthesis of novel pyrazine cnucleosides

Abstract A novel 2′deoxyβDribofuranosyl pyrazine Cnucleoside ( 6 ) was synthesized via a Stereospecific palladium(0)mediated crosscoupling reaction. The βconfiguration of this nucleoside was established by NOE analysis and the formation of a 5,5′anhydro nucleoside 5 . The compound 4a , obtained via the crosscoupling reaction and selective deprotection, is a versatile intermediate for the preparation of other pyrazine Cnucleoside analogues

A further investigation of the stannic chloride-catalyzed condensation reaction of 1-hexene and 1,2,3,5-tetra-O-acyl-β-d-ribofuranoses

Abstract The reaction of 1-hexene with either 1- O -acetyl-2,3,5-tri- O -benzoyl-β- d -ribofuranose ( 5b ) or 1,2,3,5-tetra- O -acetyl-β- d -ribofuranose ( 5a ) in the presence of stannic chloride leads to the formation of a complex mixture of products. By a combination of 1 H-n.m.r. and mass spectroscopy, the products were shown to be anomeric and diastereomeric mixtures of the 8,9,11-tri- O -acyl-protected derivatives of 7,10-anhydro-1,2,3,4,5,6-hexadeoxy- d - allo ( altro )-undec-4-enitol ( 1 ) and 7,10-anhydro-5-chloro-1,2,3,4,5,6-hexadeoxy- d - allo ( altro )-undecitol ( 2 ). The α anomer of 1 was the predominant anomer, whereas the α and β anomers of 2 were present in approximately equal amounts. It was found that 2 was not formed when trimethylsilyl trifluoromethanesulfonate was used as the catalyst instead of stannic chloride. The acyl-protected sugar 3,6-anhydro-2-deoxy- d - allo ( altro )-heptose ( 3 ), prepared by ozonolysis of 1 , reacted with tert -butoxycarbonylmethyltriphenylphosphorane to give tert -butyl trans -5,8-anhydro-6,7,9-tri- O -acetyl-2,3,4-trideoxy- d - allo ( altro )-non-2-enanate ( 4 ). The basicity of the ylide was sufficient to cause anomerization and resulted in an α,β ratio of 5:1 in the product, 4 .

A novel method for the synthesis of 6,7-unsubstituted pyrrolo[3,2-]pyrimidines

Abstract The synthesis of 2,4-dimethoxypyrrolo[3,2- d ]pyrimidine ( 4 ) is described. This facile, 3-step synthesis involves the bromination of 2,4-dimethoxy-6-methyl-5-nitropyrimidine ( 1 ), and the subsequent conversion of compound 1 into compound 4 .

Certain 8-amino-9-(benzyl)guanines as potential purine nucleoside phosphorylase inhibitors

Abstract Several 8-amino-9-(benzyl)guanines were selected for synthesis as potential purine nucleoside phosphorylase (PNP) inhibitors on the basis of the Topliss decision tree. These compounds were prepared by the treatment of oxazolo[5,4- d ]pyrimidine intermediates with potassium carbonate in a 1-pot reaction. All compounds were evaluated for PNP inhibitory activity using an in vitro enzyme inhibition assay. The extent of binding to PNP appeared to be influenced by the presence of electron donating substituents on the phenyl ring of the benzyl group. None of the tested compounds were more active than the parent compound, 8-amino-9-benzylguanine. The inhibitory activity seems to be most likely -σ-dependent.

A rapid and sensitive screening method for the detection of anti-2-acetylaminofluorene immunoglobulins

A method is described in which anti-2-acetylaminofluorene immunoglobulins may be detected using a simple and sensitive screening procedure. The method is based on immunoglobulin binding of an 125I derivatized 2-aminofluorene radiotracer. Tracer binding is not isotype specific, and thus the method is useful for the detection of either IgG or IgA. Competitive binding experiments with the radiotracer were used to determine the specificity of immunoglobulin response by measurement of cross-reactivity with related ligands. This method allows quantitation of the immune response to the carcinogen in serum and other biological fluids (i.e., intestinal secretions).