Kinetic resolution of ß-substituted olefinic carboxylic acids by asymmetric bromolactonization.

A strategically novel kinetic resolution of ß-substituted olefinic carboxylic acids is developed by asymmetric bromolactonization using an organocatalyst, 4-tBuPh-tris 1b. The cyclization stage, which provides δ-lactone, is proposed to be operative for discrimination of each enantiomer of carboxylic acids.

Preparation of THP-ester-derived pyridinium-type salts and their reactions with various nucleophiles.

Nucleophilic substitution at the anomeric positions of tetrahydropyranyl (THP) and related carbohydrate-derived esters that proceeded through pyridinium-type salt intermediates have been developed. Treatment of the 6-substituted α-acetoxy-tetrahydropyrans with TMSOTf (TMS=trimethylsilyl) and 2-substitutited pyridines, such as 2-p-tolylpyridine and 2-methoxypyridine, led to the efficient generation of cis-pyridinium-type salts. These salts reacted with various nucleophiles, such as alcohols, azides, and organozinc reagents, to form nucleophilic-substitution products. A characteristic feature of these processes was that they took place under mild conditions, which did not affect acid-labile protecting groups. Furthermore, the reactions that employed azides and C-nucleophiles generated 2,6-trans products with high degrees of stereoselectivity.

C3-symmetric trisimidazoline-catalyzed enantioselective bromolactonization of internal alkenoic acids.

A method for conducting enantioselective bromolactonization reactions of trisubstituted alkenoic acids, using the C(3)-symmetric trisimidazoline 1 and 1,3-dibromo-5,5-dimethyl hydantoin as a bromine source, has been developed. The process generates chiral δ-lactones that contain a quaternary carbon. The results of studies probing geometrically different olefins show that (Z)-olefins rather than (E)-olefins are favorable substrates for the process. The method is not only applicable to acyclic olefin reactants but can also be employed to transform cyclic trisubstituted olefins into chiral spirocyclic lactones. Finally, the synthetic utility of the newly developed process is demonstrated by its application to a concise synthesis of tanikolide, an antifungal marine natural product.

Facile preparation of oxazole-4-carboxylates and 4-ketones from aldehydes using 3-oxazoline-4-carboxylates as intermediates.

A novel 2-step synthesis of oxazole-4-carboxylates from aldehydes was developed, which is characterized by the utilization of 3-oxazoline-4-carboxylates as synthetic intermediates. The facile preparation of 4-keto-oxazole derivatives from 3-oxazoline-4-carboxylates based on their interesting reactivity toward Grignard reagents is also described.

Nanotransportation system for cholera toxin in Vibrio cholerae 01.

Vibrio cholerae (V. cholerae) cholera toxin (CT), which causes a severe watery diarrheal illness, is secreted via the type II secretion machinery; it remains unclear, however, how this toxin is transported toward the machinery. In this study, we determined that the pH-dependent intrabacterial transport system correlates with the priming of CT secretion by V. cholerae. The secretion and production of V. cholerae treated at different pHs were examined by enzyme immunoassay. The localization of the CT was analyzed by immunoelectron microscopy. The CT secretion level rapidly increases in the alkaline-pH-treated V. cholerae but does so more slowly in neutral- and acidic-pH-treated V. cholerae. The CT was found to be densely localized near the membrane in the alkaline-pH-treated bacterial cytoplasm, suggesting that the CT shifts from the center to the peripheral portion of the cytoplasm following an extracellular rise in pH. The shift was observed in V. cholerae treated at alkaline pH for more than 10 min. The pH treatment did not enhance CT production at the same stage at which secretion and intrabacterial transport of the CT were enhanced. We propose that V. cholerae possesses a pH-dependent intrabacterial nanotransportation system that probably accelerates priming for CT secretion.