A rapid and mild esterification method using carboxylic 2,4,6-trichlorobenzoic anhydrides in the presence of 4-dimethylaminopyridine was developed. The method was also successfully applied to the synthesis of large-ring lactones, including Dl-2,4,6-tridemethyl-3-deoxymethynolide.

A remarkable effect of HMPA was observed in the reduction of organic halides with a SmI2-THF solution. Various types of organic halides were reduced rapidly to the corresponding alkanes in almost quantitative yields under mild reaction conditions.

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The MICs of rabeprazole sodium (RPZ), a newly developed benzimidazole proton pump inhibitor (PPI), against 133 clinical Helicobacter pylori strains revealed a higher degree of activity than the another two PPIs, lansoprazole and omeprazole. Time-kill curve assays of RPZ, when combined with amoxicillin, clarithromycin, or metronidazole, disclosed that synergistic effects were demonstrated in combination with each antibiotic examined. Moreover, no apparent antagonistic effect appeared among all of the strains tested.It is well known that Helicobacter pylori is associated with gastric disorders, such as gastritis, and the gastric or duodenal ulcer (2,5,8,15,21). The combination chemotherapy, i.e., amoxicillin (AMC) plus clarithromycin (CAM) or metronidazole (MNZ) with a proton pump inhibitor (PPI) is now widely recommended for eradication chemotherapy (1,3,4,6,9,13,14,16 ATPase, and preliminary studies demonstrate that RPZ produces a potent and long-lasting inhibition of gastric acid secretion and a low level of hypergastrinemia (3,17,20). A novel RPZ demonstrating a chemical structure of C 18 H 20 N 3 SNa with a molecular weight of 381.43, as shown in Fig. 1, was developed in 1997 and has been proven to be effective against H. pylori strains, like other PPIs, such as lansoprazole (LPZ) and omeprazole (OPZ) (11,19). It has been demonstrated to act as an irreversible noncompetitive inhibitor of the enzyme urease that is an important virulence factor of pathogenicity of gastric H. pylori (17,20). The in vivo evaluation study of RPZ has recently been reported (18). However, no in vitro data has been available to date concerning the interaction studies of RPZ in combination with some kinds of antibiotics. Therefore, we tried to evaluate its bactericidal activity when combined with an antibiotic compound against H. pylori strains by the time-kill curve assay (10). We at first determined the in vitro activities of RPZ and its thioether (TH) derivative, RPZ-TH, together with OPZ and LPZ.The 133 H. pylori strains tested were recent clinical isolates from different patients with chronic gastritis and gastric and/or duodenal ulcer during the 2 years between April 1996 and March 1998, at the Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan. In addition, two reference strains, H. pylori NCTC 11637 and NCTC 11916, were also included in this study. All of the strains examined were preserved in Microbank (Pro-Lab Diagnostic, Richmond Hill, Ontario, Canada) vials in a deep freezer at Ϫ83°C.The antimicrobials and PPIs used were as follows: AMC from Meiji Seika Kaisha, Ltd., Tokyo, Japan; CAM from Taisho Pharmaceuticals, Co., Ltd., Tokyo, Japan; MNZ from Shionogi & Co., Ltd., Tokyo, Japan; RPZ and its derivative, RPZ-TH, from Eisai Pharmaceuticals Co., Ltd, Tokyo, Japan; LPZ from Takeda Chemical Industries, Ltd., Osaka, Japan; and OPZ from Astra Japan Ltd., Tokyo, Japan.In determining the MICs, twofold serial dilutions of each drug were made in 50 l of brucella broth (BBL Microbiology Systems Inc., Cockey...

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