Gold-Catalyzed Benzylic Azidation of Phthalans and Isochromans and Subsequent FeCl3-Catalyzed Nucleophilic Substitutions.

The benzylic positions of the phthalan and isochroman derivatives (1) as benzene-fused cyclic ethers effectively underwent gold-catalyzed direct azidation using trimethylsilylazide (TMSN3) to give the corresponding 1-azidated products (2) possessing the N,O-acetal partial structure. The azido group of the N,O-acetal behaved as a leaving group in the presence of catalytic iron(III) chloride, and 1-aryl or allyl phthalan and isochroman derivatives were obtained by nucleophilic arylation or allylation, respectively. Meanwhile, a double nucleophilic substitution toward the 1-azidated products (2) occurred at the 1-position using indole derivatives as a nucleophile accompanied by elimination of the azido group and subsequent ring opening of the cyclic ether nucleus produced the bisindolylarylmethane derivatives.

FeCl3-catalyzed self-cleaving deprotection of methoxyphenylmethyl-protected alcohols.

4-Methoxyphenylmethyl ethers are widely utilized as alcohol protecting groups. FeCl3 effectively catalyzes the deprotection of methoxyphenylmethyl-type ethers in a self-cleaving manner to produce oligomeric derivatives and alcohols. Remarkably, the highly pure mother alcohols can be obtained without silica gel column chromatography by using the 2,4-dimethoxyphenylmethyl group as a protective group.

Chemoselective and direct functionalization of methyl benzyl ethers and unsymmetrical dibenzyl ethers by using iron trichloride.

Methyl and benzyl ethers are widely utilized as protected alcohols due to their chemical stability, such as the low reactivity of the methoxy and benzyloxy groups as leaving groups under nucleophilic conditions. We have established the direct azidation of chemically stable methyl and benzyl ethers derived from secondary and tertiary benzyl alcohols. The present azidation chemoselectively proceeds at the secondary or tertiary benzylic positions of methyl benzyl ethers or unsymmetrical dibenzyl ethers and is also applicable to direct allylation, alkynylation, and cyanation reactions, as well as the azidation.

Iron-catalyzed chemoselective azidation of benzylic silyl ethers.

Azidation: siloxy groups derived from secondary and tertiary benzyl alcohols can be transformed into azide groups at room temperature using TMSN(3) in the presence of an iron catalyst (TMS=trimethylsilyl). Secondary and tertiary benzylic silyl ethers can be transformed in the presence of primary silyl ethers, and other reactive functional groups, such as alkyl chlorides, α,β-unsaturated esters, and aldehydes, are stable under the reaction conditions.

Possible role of cysteine-S-conjugate β-lyase in species differences in cisplatin nephrotoxicity.

To better understand species differences in cisplatin nephrotoxicity, we focused on renal cysteine-S-conjugate β-lyase (C-S lyase), which may play a crucial role in the metabolism of platinum (Pt)-cysteine conjugates. Aminooxyacetic acid hemihydrochloride (AOAA), an inhibitor of C-S lyase, reduced renal injuries due to cisplatin in rats, suggesting involvement of C-S lyase. On day 5 following a bolus cisplatin injection, three species showed in vivo nephrotoxic potentials in the order of rats>mice=rabbits (the highest to lowest), based on body surface.

Clinicopathological aspect of dysglycemia in naive and diabetic rats induced by the fluoroquinolone antibacterial gatifloxacin.

To ascertain the clinicopathological process underlying dysglycemia induced by the fluoroquinolone antibacterial gatifloxacin (GFLX), we orally administered 100 or 300 mg/kg/day to male clinically healthy (naive) or spontaneous type II (diabetic) Goto-Kakizaki rats for 15 days (days 1 to 15). Treatment of naive rats with GFLX led to decreased blood glucose concentrations at 100 mg/kg/day on day 1. In diabetic animals, markedly increased blood glucose concentrations were noted from 100 mg/kg/day on day 3, and all of the animals given 300 mg/kg/day died or were killed because of moribund conditions by day 9.