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Objective The effect of tonicity changes in nebulizer solutions and irrigations on nasal mucosa is not well known. The present study aims to determine the basic mechanism of hypertonic solution on airway epithelial barrier. Study design and setting We investigated the electrical potential difference (PD) that is influenced by both active transport and the transepithelial electrical resistance of the epithelial mucosa in the human nose in vivo. The short circuit current (SCC) revealed net ion transport across the epithelium in the guinea pig trachea in vitro. Finally, the size dependency of macromolecules across the tracheal mucosa was determined in vitro using FITC-labeled dextrans of different sizes. Results PD was significantly decreased after topical application of hypertonic solution both in human and in guinea pig nose. SCC was significantly decreased after application of hypertonic solution. The transport of these dextrans from the basolateral to the apical side was not increased significantly after apical application of hypertonic saline. Conclusions Hypertonic saline enhances the electrical permeability of the airway epithelial mucosa but not transport of macromolecule in the short term.

The stereoselective synthesis of catechin and epicatechin dimers is achieved by intermolecular condensation using SnCl4 as Lewis acid.

The first synthesis of cyclic polyglycerols as pure compounds is based on an intramolecular cyclization method.

A series of enantiomerically pure 4-substituted bisoxazolines la-f , 2c, and 2e was prepared from naturally derived or synthetic amino alcohols and malonyl dichloride derivatives. The formation of the bisoxazolines was accomplished in two stages: (1) preparation of the bis-amides of the malonyl derivatives with the amino alcohols and (2) cyclization of the hydroxy amides 4 by either of two general protocols; (1) heating with thionyl chloride in toluene or (2) formation of the bismesylate and then heating with aqueous or alcoholic base. The latter procedure was found to be more reliable especially for bisoxazolines with bulky substitutents at C(4). The C(4) trityl-substituted hydroxy amide 4f produced the bis(acy1aziridine)lO by cyclization on the nitrogen atom using KOWMeOH, but afforded the desired bisoxazoline I f by the action of SOClflt3N. The synthesis of the nonnaturally derived amino alcohols using the Evans asymmetric azidation procedure is also described.

Three novel fouorinated analogues of huperzine A ( 1 ), (±)-12,12,12-trifluorohuperzine A ( 2 ), (±)-14,14,14-trifluorohuperzine A ( 3 ), and (±)-12,12,12,14,14,14-hexafluorohuperzine A ( 4 ), have been synthesized by employing TMSCF 3 as a trifluoromethylating agent. These analogues were found to still retain anti-acetylcholinesterase activity.

The first total synthesis of 16-membered tetraene macrolide antibiotic hydrolidin, a potent and relatively specific inhibitor of the vacuolar ATPases, has been achieved, incorporating macrolactonization by the modified Yamaguchi method and fragment assembly aldol reaction to establish the C17-C18 bond as key steps.

In order to establish a mild conversion method of primary amides to nitriles, various types of carboxamides were treated under Swern oxidation conditions, (COCl)2-DMSO and Et3N, as a dehydrating agent to obtain desired nitriles in 75–96% yields.

An approach to 2,2,2-trifluoroethylidene derivatives from ketones was explored by employing the Corey-Winter's reductive elimination of 4-trifluoromethyl-1,3-dioxolane-2-thiones to 2,2,2-trifluoroethylidene derivatives as a key step. The 1,3-dioxolane-2-thione derivatives were readily prepared from ketones in five steps by sequential formation of O-silylated cyanohydrins, reduction, addition of trifluoromethyltrimethylsilane, desilylation, and formation of the 1,3-dioxolane-2-thione system.

We have succeeded in one-pot preparation of perfluoroimidates at −78 °C by employing the dehydration of perfluoroamide under the “activated” dimethyl sulfoxide (DMSO) species followed by in situ nitrile trapping with alcohols. MPM and DMPM perfluoroimidates can be used to protect alcohols in place of the trichloroacetimidate with excellent chemical properties and in comparable yields.

Three pyrimidinylpropanamide antibiotics sparsomycin ( 1 ), sparoxomycins A1, A2 ( 2, 3 ), and also six analogues ( 4–9 ) have been synthesized by employing asymmetric sulfide oxidation conditions as a key step. Sparsomycin ( 1 ) and its alkyl analogues ( 5–7 ) showed higher morphological reversion activities on src ts NMR cells than 2 and 3 .

The one-pot preparation of allyl, epoxy and glycosyl perfluoroimidates and their reaction are described. Volatile perfluoronitriles were generated from perfluoroamides with an ‘activated’ dimethyl sulfoxide (DMSO) species at −78°C. Allyl, epoxy and glycosyl perfluoroimidates were prepared in 44–92% yield following in situ nucleophilic addition of alcohol and sugar derivatives to nitriles. The obtained trifluoroacetimidates were more stable than the trichloro analogue and were easily purified by SiO 2 column chromatography and/or distillation. The 3,3-sigmatropic rearrangement of allylic analogues, acid-catalyzed cyclization of the epoxy analogues and glycosylation of sugar analogues were studied comparing with their corresponding trichloroacetimidates. The trifluoroacetimidates were considerably less reactive than trichloroacetimidates due to their electron-withdrawing substituents on the imidate carbon.

In order to establish a simple common methodology for the highly stereoselective and efficient synthesis of macrolide aglycones, 12-membered ring methynolide and 16-membered ring tylonolide were synthesized from D-glucose via the synthesis of respective fragments followed by their coupling (esterification by the Yamaguchi method) and cyclization by the Wittig-Horner reaction under Nicolaou's conditions. This method was extended to the synthesis of 14-membered ring pikronolide and, together with conformational control of macrolide rings, to some typical 16-membered ring aglycones such as carbonolides, leuconolides, maridonolides, etc. A new synthesis of erythronolide A via an extremely efficient macrolactonization by virtue of conformational control and super activation of the seco-acid is also described.

The polarization characteristics of poly(tetrafluoroethylene)-bonded Raney nickel hydrogen- and silver oxygen-electrodes have been measured as a function of the thickness of the catalyst layer, and the polarization curves of these electrodes have been analyzed on the basis of the electrolyte film model. The observed polarization curves were divided into several segments and a linear polarization-current equation, derived from the model, has been applied to each segment. The performance of the electrodes approaches asymptotically to an upper limit with the thickening of the catalyst layers. The profiles of the faradayic current density across the electrode wall have been estimated for both electrodes. In contrast with the almost flat profiles of the Raney nickel electrodes, the current densities for the silver electrodes are localized on the liquid side of the electrodes; a thin area of the catalyst layer ranging from the electrode-face/electrolyte interface to 5.3×10−3cm distance sustains most of the load...

In order to establish a mild protection method for hydroxy functions with a MPM (4-methoxybenzyl) group, various types of hydroxy compounds were treated with MPM trichloroacetimidate in the presence of an acid catalyst. A catalytic amount (0.3 mol %) of trifluoromethanesulfonic acid was most effective and the reaction was completed within 40 min at room temperature even for highly sterically hindered hydroxy groups.

New protecting groups for the hydroxy function, 3-methoxybenzyl (3-MPM) and 3, 5-dimethoxybenzyl (3, 5-DMPM) groups are slowly removed by DDQ oxidation at room temperature and distinguished from readily removable 4-methoxybenzyl (MPM). They are stable to strong acids.