Chiral sulfoxides have provided useful methods for asymmetric carbon-carbon bond formations. Among them chiral α, β-unsaturated sulfoxides have offered effective dienophiles in asymmetric Diels-Alder reactions. In the continuation of this study aiming at exploring a conceptually new approach to such sulfoxides, we focused on a (2-exo-hydroxy-10-bornyl) sulfinyl moiety instead of a p-tolylsulfinyl group which has widely been employed as a chiral auxiliary. The use of this chiral auxiliary (i. e. (2-exo-hydroxy-10-bornyl) sulfinyl) realized not only a facile preparation of chiral α, β-unsaturated sulfoxides but also the synthesis of chiral α-sulfinylmaleate and α-sulfinylmaleimide derivatives which effected Diels-Alder cycloadditions with high diastereoselectivity. Especially the α-sulfinylmaleimides readily reacted with the Diels-Alder dienes with rather low reactivity such as furan, to afford the corresponding Diels-Alder adducts under conventional conditions. The chirally functionalized adducts derived from the Diels-Alder reactions were transformed into some, biologically important natural products.
The development of new methodologies for the stereocontrolled synthesis of complex molecules is very important for the efficient synthesis of therapeutic agents. In this review, 1) the stereocontrolled synthesis of exocyclic olefins using arene·Cr (CO)3-catalyzed 1, 4-hydrogenation of conjugated diene and its application to the synthesis of prostacyclin analogs, 2) new catalytic activities of arene·Cr (CO)3 as a hydrogenation catalyst, 3) the stereocontrolled synthesis of silyl dienol ethers and dienamides using arene·Cr (CO)3-catalyzed isomerization, and 4) a novel carbon-carbon bond-forming reaction through η5-pentadienylchromium complexes, are described.
The effect of simultaneous administration of Enterued[○!R], an elemental diet, which is composed of oligopeptides (egg white hydrolyzate), on the orally active cefems was investigated. Ceftibuten (CETB) administered together with Enterued[○!R] to man was excreted slower in the urine. AUC from the plasma concentrations of CETB after the oral administration with Enterued[○!R] was markedly decreased compared to that without Enterued[○!R] in rat. In contrast, neither urinary excretion of cephalexin (CEX) in man nor the AUC from the plasma profile of CEX in rat was changed by Enterued[○!R]. Furthermore, the disappearance, tissue accumulation, net absorption of CETB from the rat jejunal loop were significantly inhibited by Enterued[○!R]. However, the net absorption of CEX has no alternation in the presence of Enterued[○!R], although the apparent disappearance decreased on the basis of the diminishment of tissue accumulation. Additionally, Hepan ED[○!R], which is an elementary diet composed of amino acids, and the mineral solution containing neither peptides nor vitamins have also exhibited the decreasing effect on the CETB absorption behaviour. These results suggested that the inhibitory effects of Enterued[○!R] on the absorption of these antibiotics were not due to the inhibition of peptide-transport systems.
As a series of study on the evaluation of Alismatis Rhizoma and the chemical characterization of the processing, a quantitative method by high performance liquid chromatography (HPLC) for ten triterpene constituents, alisols A, A monoacetate, B, B monoacetate, E 23-acetate, F, and G and 13, 17-epoxyalisol A, 11-deoxyalisols B and B 23-acetate, has been developed. By the use of this HPLC method, the contents of these triterpenes in various Alismatis Rhizoma and the fresh rhizoma of Alisma orientale JUZEPC. originaed from in China, Taiwan, and Japan were examined. Furthermore, the chemical change of the triterpene constituents during the drying process of the rhizoma of Alisma orientale has been investigated and it was found that the bioactive triterpenes of Alismatis Rhizoma such as alisol A and alisol A monoacetate were artificially formed during the drying process.
To search for possible anti-tumor promoters, we carried out a primary screening of fourteen kampo prescriptions utilizing their possible inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation which is induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). In these prescriptions, shouseiryu-to exhibited the most significant inhibitory effect on the EBV-EA activation. Furtheremore, two-stage carcinogenesis of mouse skin tumors induced by 7, 12-dimethylbenz [α] anthracene (DMBA) and TPA, and mouse pulmonary tumors induced by 4-nitroquinoline-N-oxide (4NQO) and glycerol were strongly inhibited by shouseiryu-to.
In the dissolution test of tablets prepared by the direct compression of chitosan with 10% sodium alginate (NaAlg), the release of theophylline was extended independently of the medium pH. The drug release mechanism of the tablet was investigated by measuring the dissolution behavior of such excipients as chitosan and NaAlg. It was shown that at the lower pH the drug release was accompanied with the dissolution of chitosan, while at the neutral pH it was controlled by the gelation and dissolution of NaAlg. Further more by the oral administration of the tablet to beagle dogs, the sustained release of theophylline was also confirmed by some bioavailability parameters. Thus the chitosan tablet with 10% NaAlg was expected to be a pH-independent sustained release dosage form.
From the leaves of Scutellaria alpina L., four new neo-clerodane diterpenes (1-4) were isolated. The structures of 1-4 were shown to be (4S)-19-acetoxy-8β-hydroxy-6α-benzoyloxy-4, 18-epoxy-neo-cleroda-11, 13-dien-15, 16-olide, (4S)-19-acetoxy-8β-hydroxy-6α-tigloyloxy-4, 18-epoxy-neo-cleroda-11, 13-dien-15, 16-olide, (4S, 11S)-11-acetoxy-8β, 19-dihydroxy-6α-tigloyloxy-4, 18-epoxy-neo-clerod-13-en-15, 16-olide, and (4S)-19-acetoxy-8β-hydroxy-6α, 7β-dibenzoyloxy-4, 18-epoxy-neo-cleroda-11, 13-dien-15, 16-olide, respectively, by the chemical and spectral data.
The reaction of ethyl 3-aryl-2-nitroacrylate (1a : aryl=3-methoxyphenyl) with toluene in the presence of titanium tetrachloride gave 4-(4'-methyl-phenyl)-4H-1, 2-benzoxazine (3) in a 44.2% yield. The acrylate 1a reacted with dichloromethane in the presence of titanium tetrachloride to give 5-methoxy-salicylaldehyde (2a) in a 61.8% yield. Therefore, 2a was presumed to be formed via an intermediate 4H-1, 2-benzoxazine (3'), followed by ring opening to quinone methide and cyano formate. In a similar reaction using both toluene and dichloromethane, 1 bearing a 2-naphthyl group gave a dimer of quinone methide and 1-hydroxy-2-naphthaldehyde via 4H-naphth [2, 1-e]-1, 2-oxazine, respectively.