2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazoles (2, sulfides) exhibit antibacterial properties that are selective for Helicobacter spp., but they also have an inherent susceptibility to metabolic oxidation to furnish 2-[[(2-pyridyl)methyl]sulfinyl]-1H-benzimidazoles (1), which act as proton pump inhibitors (PPIs). We have discovered five compounds with retained antibacterial potency and selectivity in which the overall framework of the sulfides 2 could be kept intact while structural modifications were made to remove PPI activity. These compounds, 2-[((2-methyl-3-(2-(2-(2-methoxyethoxy)ethoxy)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (79), 2-[((2-methyl-3-(2-(2-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)ethoxy)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (80), 2-[((2-methyl-3-((2-morpholino)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (86), 2-[[[2-methyl-3-[2-(2-methyl-5-nitroimidazol-1-yl)ethylthio]phenyl]methyl]thio]-1H-benzimidazole (88), and 2-[[[2-methyl-3-[2-(1,2,4-triazol-1-yl)ethylthio]phenyl]methyl]thio]-1H-benzimidazole (89), had minimum bactericidal concentrations (MBCs) of 0.5, 0.5, 1, 2, and 4 microg/mL, respectively. The reported compounds are bactericidal with MBCs within 1 order of magnitude of MBCs of clinically used antimicrobials such as clarithromycin (0.1 microg/mL) or metronidazole (2-4 microg/mL) but differ from these inasmuch that they have an extremely narrow spectrum activity and appear to be species specific.

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A mechanistic model for t h e addition of lithium dimethylcuprate to enoates and enones is proposed on t h e basis of chemical and NMR-spectroscopic studies. The first s t e p of t h e reaction is t h e reversible formation of a copper($ alkene n-complex by coordination of t h e C -C group to one of t h e copper a t o m s in t h e dimeric cluster s t r u c t u r e (Me Culi&. The following steps lead to t h e irreversible formation of t h e new carbon-carbon bond. With chiral substrates t w o diastereomeric n-complexes a r e postulated, t h e stereoselectivity being determined by t h e relative r a t e s for their irreversible decay. In t h e reaction between methyl S-ortho-dimethylaminoethylcinnamate, 10, and lithium dimethyl-and lithium diphenylcuprate t h e diastereomeric product ratios a r e ca 5: 1. 2

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