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A practical approach to radical C–H bond functionalization by the photolysis of a hypervalent iodine(III) reagent is presented. The photolysis of [bis(trifluoroacetoxy)iodo]benzene (PIFA) leads to the generation of trifluoroacetoxy radicals, which allows the smooth transformation of various alkylbenzenes to the corresponding benzyl ester compounds under mild reaction conditions.

The X-ray absorption fine structure (XAFS) spectroscopy was used to analyze the chemical state conversion of the Ni species in SiO2-supported Ni catalysts which were prepared by the impregnation me...

Two new phenylpropanoid glycosides (I) and (II) are isolated along with several known substances from leaves and stems of the North American title plant.

Ethyl 3-chloro-3-(3, 4-dichlorophenylthio)propanoate (8) reacted with electron-rich arenes in the presence of titanium tetrachloride to give the Friedel-Crafts products 10a-13a. Reactions of 8 with 1-trimethylsilylalkynes 14a-d were effected with aluminum chloride to afford the substitution products 15a-d. Some chemical transformations of the products are also described.

1,4-Bis(hydroxymethyl) Dewar benzenes were prepared in five steps from dimethyl acetylenedicarboxylate in ca. 10% overall yield and rates of their aromatization were measured: dichloro substitution at both the 2,5- and 2,6-positions led to substantial deceleration of the isomerization.

The reaction of an alcohol with a trialkyl phosphite in the presence of pyridinium bromide perbromide and triethylamine afforded the phosphoric triester in good yield, which can be transformed to the phosphoric monoester or diester. The method was applied to selective phosphorylation aiming at a convenient of phosphatidyl myo - inositol derivatives.

Reduction of aldehydes and ketones with 2-propanol proceeded efficiently over silica-supported zirconium catalyst, and the corresponding alcohols were obtained in high yields. In the reduction of aldehyde, the acetalization did not occur and the side reaction, the aldol condensation, was inhibited.

In order to improve the oral bioavailability (BA) of 2-butyl-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimid azole - 7-carboxylic acid (3: CV-11194) and 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4- yl]methyl]-1H-benzimidazole-7-carboxylic acid (4: CV-11974), novel angiotensin II (AII) receptor antagonists, chemical modification to yield prodrugs has been examined. After selective tritylation of the tetrazole rings in 3 and 4, treatment of N-tritylated benzimidazole-7-carboxylic acids (6, 7) with a variety of alkyl halides, followed by deprotection with hydrochloric acid, afforded esters of 3 and 4. Mainly 1-(acyloxy)alkyl esters and 1-[(alkoxycarbonyl)oxy]alkyl esters, double ester derivatives, were synthesized. Their inhibitory effect on AII-induced pressor response in rats and oral BA were investigated. (Pivaloyloxy)methyl and (+/-)-1-[[(cyclohexyloxy)-carbonyl]oxy]ethyl esters of 3 and 4 showed marked increases in oral bioavailability which significantly potentiated the inhibitory effect of the parent compounds on AII-induced pressor response. Among them, (+/-)-1-[[(cyclohexyloxy)carbonyl]oxy]ethyl 2- ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimida zole- 7-carboxylate (10s, TCV-116) was selected as a candidate for clinical evaluation.

A novel series of heterocyclic compounds I bearing two acidic funcitonalities, a carboxyl group and a tetrazole ring, was prepared and evaluated for in vitro and in vivo angiotensin II (AII) antagonistic activity. These compounds showed significantly more potent All antagonistic activities than the parent compounds without the carboxyl groups. This structure-activity relationhsip (SAR) study revealed the importance of the carboxyl group attached to the heterocyclic moieties especially for insurmountable antagonism and enhancement of in vivo (po) activity.

N[sub 2][sup +] and As[sup +] ions have been implanted in [beta]-SiC/Si wafers to form n-type layers in the substrates. Postimplant annealing was carried out at a temperature in the range of 400 to 1,200 C. The crystalline properties for implanted [beta]-SiC layers have been examined by an electron diffraction method and also by Rutherford backscattering spectroscopy. The electrical properties of n-type layers formed in the SiC have been evaluated by Hall-effect measurements. The experimental results obtained from the present work show that the recrystallization of the implantation-induced amorphous layer and the electrical activation of implanted atoms are initiated by annealing of 800 C. It is also shown that hot implantation is more effective for achieving the high electrical activation of implanted atoms as compared with room temperature implantation. A highly doped n-type [beta]-SiC layer can be formed by N-implantation at 400 C and by subsequent annealing at 1,200 C.

As part of a search for potent and long-lasting angiotensin converting enzyme (ACE) inhibitors, various types of N-[(1S)-1-carboxy-5-(4-piperidyl)pentyl]-L-alanine derivatives (7a, 8-11) were prepared. The key synthetic intermediate, N-[(1S)-5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]-L-alanine (17a), was synthesized by asymmetric reduction of the α-oxoester (13) with Lactobacillus paracasei subsp. paracasei followed by a substitution reaction with tert-butyl L-alaninate (15) and subsequent treatment with hydrogen chloride. Compounds 7a and 8-11 showed potent and long-lasting ACE-inhibitory activity in rats.

A new cyanoglucoside, purshianin (1), was isolated together with a known cyanoglucoside, menisdaurin (2a), from stems of Purshia tridentata DC. (Rosaceae) collected in Oregon, U.S.A. and the structure was established as (4S, 6S)-(Z)-6-(β-D-glucopyranosyloxy)-4-hydroxy-2-cyclohexene-Δ1, α-acetonitrile (1) based on chemical and spectral evidence. Notably, the absolute structure of 1 and the revised stereostructure (2), (4S, 6R)-(Z)-6-(β-D-glucopyranosyloxy)-4-hydroxy-2-cyclohexene-Δ1, α-acetonitrile for menisdaurin were decided based on combined studies of difference NOE spectra and Dreiding model inspection.

1,3-Oxathiolanes were prepared via electrochemical chemoselective α-acetoxylation of β′-hydroxy sulfides and were converted into 4-acetoxy-1,3-oxathiolanes, precursors of 2′,3′-dideoxy-3′-oxa-4′-thioribonucleosides, by the electrolytic acetoxylation of the 1,3-oxathiolane or by Pummerer rearrangement via sulfoxide.

The synthesis and angiotensin II (AII) antagonistic activity of 2-substituted benzimidazole-7-carboxylic acids ( 8 ) bearing a novel acidic bioisostere, a 5-oxo-1,2,4-oxadiazole ring, are described. These compounds had in vitro and in vivo AII receptor antagonistic activity comparable to that of tetrazole analogs. The representative compound, TAK-536 ( 8e ) is a potent, orally active and specific AII receptor antagonist.

From a whole plant of a fern, Diplazium subsinuatum (WALL. ex HOOK. et GREV.) TAGAWA, two new hopane-triterpene glycosides termed diplaziosides I and II were isolated together with a known hopane-triterpene glycoside named glycoside C (1). The structures of diplaziosides I and II were established as 24-O-[α-L-arabinofuranosyl-(1→2)]-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranosyl-hopan-28,22-olide(2) and (22R)-17-hydroxy-24-O-[α-L-arabinofuranosyl-(1→2)]-β-D-glucopyranosyl-28,22-carbonyloxy-hopan-30-oic acid (3), respectively, on the basis of spectral evidence. In addition, the full 1 H- and 13 C-NMR assignments for known 1 are also reported for the first time.

The design, synthesis, and biological activity of benzimidazole-7-carboxylic acids bearing 5-oxo-1,2,4-oxadiazole, 5-oxo-1,2,4-thiadiazole, 5-thioxo-1,2,4-oxadiazole, and 2-oxo-1,2,3,5-oxathiadiazole rings are described. These compounds were efficiently prepared from the key intermediates, the amidoximes 4. The synthesized compounds were evaluated for in vitro and in vivo angiotensin II (AII) receptor antagonistic activities. Most were found to have high affinity for the AT1 receptor (IC50 value, 10-6−10-7M) and to inhibit the AII-induced pressor response (more than 50% inhibition at 1 mg/kg po). The 5-oxo-1,2,4-oxadiazole, 5-oxo-1,2,4-thiadiazole, and 5-thioxo-1,2,4-oxadiazole derivatives showed stronger inhibitory effects than the corresponding tetrazole derivatives, while their binding affinities were weaker. This might be ascribed to their improved bioavailability by increased lipophilicity. The 5-oxo-1,2,4-oxadiazole derivative 2 (TAK-536) and 5-oxo-1,2,4-thiadiazole derivative 8f showed efficient or...

Three pregnanes and two known cycloartane-type triterpenoid hydroperoxides were isolated from the leaves of Aglaia grandis . Their structures were determined using 1 H, 13 C and 2D NMR techniques. © 1997 Elsevier Science Ltd. All rights reserved

The first total synthesis of the new type of cytocydal β-carboline alkaloid oxopropaline G was achieved in 12 steps.

Polyethylene glycolated horseradish peroxidase (PEG-HRP) can catalyze one- and two-electron oxidation reactions in organic solvents as well as in aqueous buffer. Even though the oxidation of guaiacol in benzene and chlorobenzene is 5 orders of magnitude slower than in phosphate buffer, compounds I and II are involved in the catalytic cycle in organic media. Factor analysis and global fittings of rapid scan data set reveal that the formation of compound I of PEG-HRP in organic media consists of two steps (the first fast and the second slow) and suggest the involvement of a H2O2−HRP complex in the catalytic cycle. The labile precursor of compound I is stabilized when PEG-HRP reacts with hydrogen peroxide in chlorobenzene at −20 °C. The absorption spectrum of the precursor does not exhibit the features of hyperporphyrin spectrum but has a normal Soret as previously observed in R38L HRP. More importantly, compound I of PEG-HRP can be maintained for more than an hour at −20 °C in chlorobenzene.

Blockade of the action of angiotensin II (AII) has long been a target for the development of novel antihypertensive agents. We recently discovered a novel class of potent nonpeptide AII receptor antagonists, benzimidazole-7-carboxylic acids including candesartan. Candesartan is a highly potent and insurmountable AII type-1 receptor (AT1)-selective antagonist. Structure-activity relationship (SAR) studies revealed that the adjacent arrangement of a lipophilic substituent, a tetrazolylbiphenylmethyl moiety and a carboxyl group was the important structural requirement for potent AII antagonistic activity. Especially, the presence of a carboxyl group at the 7-position was found to be essential for insurmountable antagonism. To improve bioavailability of candesartan, chemical modification was examined to yield candesartan cilexetil, a prodrug of candesartan. Candesartan cilexetil is a potent and long-acting blocker that, when given once a day to patients, provides effective 24 hr blood pressure control.

Two benzophenanthrene alkaloids, 8-acetonyldihydronitidine and 8-acetonyldihydroavicine were isolated from Zanthoxylum tetraspermum stem bark along with liriodenine, sesamin, lichexanthone and (+)-piperitol-γ,γ-dimethylallylether. The species endemic to Sri Lanka, Z. caudatum, contained sesamin, savinin, liriodenine, decarine and 8-O-desmethyl-N-nornitidine. 8-Acetonyldihydronitidine and 8-acetonyldihydroavicine showed significant antibacterial activity while the former along with liriodenine was strongly antifungal. Savinin exhibited potent spermicidal activity. Both savinin and sesamin exhibited significant insecticidal activity.

We succeeded in the detection of the sitting-atop (SAT) copper(II) complex of TPP (5,10,15,20-tetraphenylporphyrin) in acetonitrile (AN) as a solvent with a very low Bronsted basicity, where two pyrrolenine nitrogens in the Cu(II)-SAT complex coordinate to the metal ion and two protons still remain on the pyrrole nitrogens. The structure parameters around the copper(II) ion in the Cu(II)-SAT complex, as determined by a fluorescent EXAFS method, suggest an axially elongated and equatorially distorted six-coordinate geometry. We measured the rates of the formation reaction of the SAT complexes for a series of transition metal(II) ions in AN using the stopped-flow technique. We propose the mechanism where there is a rapid deformation equilibrium of the porphyrin ring prior to the rate-determining step of the bond rupture of a coordinated solvent molecule on the metal(II) ion. Furthermore, we measured the rates of the deprotonation reaction of the Cu(II)-SAT complex by some Bronsted bases and indicated that the rate-determining step is the attack of the base on the proton of the pyrrole nitrogen in the SAT complex. Finally, a unified mechanism relevant to the porphyrin metalation mechanism has been proposed.

Chemical examination of the leaves of Aglaia elliptica led to the isolation of two new diamides, 10-O-acetylaglain B (1) and 4-epiaglain A (2), two known diamides, aglain A (3) and odorine (4), and three known cycloartanes (5-7). The structures of 1 and 2 were elucidated by interpretation of the spectral data.

Compounds 1 or 2 which possess dual-acting PAF antagonist/TxSI in a previous paper were modified and evaluated for the dual-acting activity. It was found that several compounds were potent dual-acting PAF antagonist/TxSI in and ex vivo. 6-(2-Chlorophenyl)-3-[4-[(E/Z)-6-ethoxycarbonyl-1-(3-pyridyl)-1-hexenyl]phenylmethyl]-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3': 4,5]thieno[3,2-f]triazolo[4,3-a]diazepine (12) is excellent orally dual-acting PAF antagonist/TxSI.

Novel ruthenium-catalyzed cycloaddition of propargylic alcohols with 2-naphthols and phenols bearing electron-donating groups via allenylidene intermediates has been developed to give the corresponding 1H-naphtho[2,1-b]pyrans and 4H-1-benzopyrans, respectively, in moderate to excellent yields with complete regioselectivity.

Novel 4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives were synthesized and evaluated for their abilities to inhibit lipopolysaccharide (LPS)-stimulated production of TNF-α in rat whole blood. Several of these compounds exhibited potent inhibitory activity.

Two new 24-ethyl,24-methyl-29-nor-lanostanes (1, 2) were isolated from the MeOH extract of leaves of Freycinetia formosana (Pandanaceae). Their structures were elucidated based on spectroscopic evidence.

Three novel furoquinoline alkaloid oxogeranyl ethers (1-3) and one known furoquinoline alkaloid (4) were isolated from the leaves of Boninia glabra, an endemic plant of the Bonin Islands. Their structures were elucidated on the basis of spectroscopic analysis.

Ruthenium-catalyzed carbon−carbon bond forming reactions between propargylic alcohols and acyclic and cyclic 1,3-conjugated dienes give the corresponding dienyne compounds in good to high yields. Only the use of thiolate-bridged diruthenium complexes promotes the catalytic reactions, where a ruthenium−alkynyl complex, a resonance structure of a ruthenium−allenylidene complex, works as a key intermediate. This carbon−carbon bond forming reaction is considered to proceed via a stepwise reaction pathway. The finding described in this article reveals another novel catalytic reactivity of chalcogenolate-bridged diruthenium complexes.

Novel ruthenium-catalyzed vinylic substitution reactions of vinylic trifluoromethanesulfonates with nucleophiles such as cyclic 1,3-diketones and alcohols have been found to give the corresponding vinylic-substituted products in good to high yields. This catalytic reaction is considered to be a new type of vinylic substitution reaction. Reactions of α-ketoacetylenes with alcohols have also been found to afford the corresponding vinylic ethers in good yields. These catalytic reactions can be explained to proceed by proposing ruthenium−butatrienylidene complexes as key intermediates. We believe that this finding will open up a further aspect of the chemistry of metal−cumulenylidene complexes.

Novel fluorescent 3,6-diaryl-4-phenyl-2-pyridone derivatives were synthesized and their fluorescent properties were investigated. These compounds emit intense brilliant blue fluorescence only in th...