Hiroko Hachiken

Reaction of indole-2,3-dicarboxylic anhydride with (3-bromo-4-pyridyl)triisopropoxytitanium: Synthesis of ellipticine

Abstract N -Benzylindole-2,3-dicarboxylic anhydride ( 1 ) was reacted with (3-bromo-4-pyridyl)triisopropoxytitanium to give 2-(3-bromoisonicotinoyl)indole-3-carboxylic acid ( 2 ) as the sole product in high yield, which could be converted to ellipticine in six steps.

Synthesis of ellipticine by reaction of 1-(4-methoxybenzyl)indole-2,3-dicarboxylic anhydride with (3-bromo-4-pyridyl)triisopropoxytitanium

Reaction of 1-benzyl- and 1-(4-methoxybenzyl)indole-2,3-dicarboxylic anhydride with (3-bromo-4-pyridyl)triisopropoxytitanium gave the corresponding 2-acylindole-3-carboxylic acids as the sole product. Deprotection of the 1-(4-methoxybenzyl) group of the 2-acylindole-3-carboxylic acid was performed by treatment with perchloric acid in acetic acid to afford 2-(3-bromoisonicotinoyl)indole, which was converted to ellipticine.

Synthesis of 3-Substituted Pyrazolo[1,5-a]pyridines by Electrophilic Reactions

Reactions of pyrazolo[1,5-a]pyridines with Eschenmosers salt, activa- ted alkenes and alkynes, and chlorosulfonyl isocyanate provided general routes to 3-substituted pyrazolo[1,5-a]pyridines such as 3-dimethylami- nomethyl-and 3-(2-nitroethyl)pyrazolo[1,5-a]pyridines, 1-phenyl-3-(py- razolo[1,5-a]pyrid-3-yl)-2-propen-1-ones, 4-(pyrazolo[1,5-a]pyrid-3-yl) -3-buten-2-one, pyrazolo[1,5-a]pyridine-3-carboxamide, and pyrazolo [1,5-a]pyridine-3-carbonitrile

A new entry to [2.3.4]cyclazines

Treatment of 2,3-dihydro-2-methyl-3-phenyl-1H- pyrazino 3,4,5-cd indolizine 2-oxides (5) with trifluoroacetic anhydride gave new heterocyclic six-membered betaines (6) which underwent 1,3-dipolar cycloaddition reaction with dimethyl acetylenedicarboxylate and maleimides in hot toluene to yield the corresponding cycloadducts (7) and (8). Treatment of the maleimide adducts (8) with p-toluenesulfonic acid in boiling acetic acid gave the [2.3.4]cyclazines (9)

Difference between the frequencies of antisecretory drug prescriptions in users of buffered vs. enteric-coated low-dose aspirin therapies.

OBJECTIVE To provide further insights on the risks of gastrointestinal (GI) complications in individuals using low-dose aspirin (LDA), we investigated the concomitant use of LDA and antisecretory drugs. Additionally, we examined the frequency distributions of prescribing sequences for LDA and antisecretory drugs. METHODS Data from a computerized prescription order entry system was analyzed at the National Cerebral and Cardiovascular Center of Japan. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pomp inhibitors (PPIs) was examined over the period from January 2001 to December 2010. Prescription sequence symmetry analyses were used to identify LDA-induced H2RAs or PPIs users. RESULTS In December 2010, PPIs accounted for 9.9% of the prescriptions for buffered LDA users and 16.1% of those for enteric-coated LDA users. Incident use of PPIs occurred more frequently among enteric-coated LDA users than buffered LDA users (17.6% vs. 11.0%, respectively). Prescription sequence symmetry analyses of PPI use revealed significant associations with enteric-coated LDA use, resulting in adjusted sequence ratios of 1.82 (95%CI, 1.11 - 3.03) and 1.87 (95% CI, 1.26 - 2.83) at intervals of 182 and 365 days, respectively. Enteric-coated LDA users tended to initiate PPI therapy on the same date more frequently than buffered LDA users (35.1% vs. 10.8%, respectively). CONCLUSIONS Our findings do not support the notion that entericcoated LDA products confer a lower risk for GI complications than buffered formulations, but may conversely imply that the risk of GI complications associated with buffered LDA is lower than that of enteric-coated LDA.

Synthesis of 2- and 3-Benzoylindoles by Friedel-Crafts Reaction of Indole-2,3-dicarboxylic Anhydrides with Anisoles

Reaction of 1-benzylindole-2,3-dicarboxylic anhydride with anisole in the presence of titanium(IV) chloride gave 2-(4-methoxybenzoyl)indole-3-carboxylic acid as the sole product. However, l-benzenesulfonylindole-2,3-dicarboxylic anhydride with anisole afforded 3-(4-methoxybenzoyl)indole-2-carboxylic acid. These carboxylic acids could be converted to the corresponding benzoylindoles.