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 of vitamin B12. 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 available1-3.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28637/1/0000451.pd

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

The synthesis of 2,4-dimethoxypyrrolo[3,2-]pyrimidine () is described. This facile, 3-step synthesis involves the bromination of 2,4-dimethoxy-6-methyl-5-nitropyrimidine (), and the subsequent conversion of compound into compound .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24161/1/0000419.pd

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

The reaction of 1-hexene with either 1-O-acetyl-2,3,5-tri-O-benzoyl-[beta]--ribofuranose (5b) or 1,2,3,5-tetra-O-acetyl-[beta]--ribofuranose (5a) in the presence of stannic chloride leads to the formation of a complex mixture of products. By a combination of 1H-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--allo(altro)-undec-4-enitol (1) and 7,10-anhydro-5-chloro-1,2,3,4,5,6-hexadeoxy--allo(altro)-undecitol (2). The [alpha] anomer of 1 was the predominant anomer, whereas the [alpha] and [beta] 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--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--allo(altro)-non-2-enanate (4). The basicity of the ylide was sufficient to cause anomerization and resulted in an [alpha],[beta] ratio of 5:1 in the product, 4.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25238/1/0000680.pd

Synthesis of 1-(2-aminopropyl)benzimidazoles, structurally related to the TIBO derivative R82150, with activity against human immunodeficiency virus.

A number of 1-(2-aminopropyl)-2-mercaptobenzimidazoles related to the TIBO derivatives R82150 have been prepared and tested for their activity against human immunodeficiency virus type 1 (HIV-1). These compounds were all modest inhibitors of the cytophatic effects of HIV-1 in vitro, but only very weak inhibitors of HIV-1 reverse transcriptase (RT).A number of 1-(2-aminopropyl)-2-mercaptobenzimidazole derivatives related to the TIBO derivative R82150 have been prepared and tested for their activity against human immunodeficiency virus type 1 (HIV-1). These compounds are all modest inhibitors of the cytopathic effects of HIV-1 in vitro, but were only weak inhibitors of HIV-1 reverse transcriptase (RT).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30886/1/0000555.pd

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).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27330/1/0000354.pd