Syntheses of [prolyl-U-14C]alacepril and its related compounds

In order to study the metabolic fate of alacepril, an anti-hypertensive agent, the 14C-labeled compound of alacepril and its related compounds were synthesized. [Prolyl-U-14C]alacepril was synthesized in over-all yield of 32.7-38.0% by the mixed anhydride condensation of L-phenylalanine with [prolyl-U-14C]DU-1163, which had been prepared from L-[U-14C]proline and N-(S-3-acetylthio-2-methylpropanoyloxy)succinimide. [Prolyl-U-14C]captopril and [prolyl-U-14C]DU-1227 were prepared in high yields by hydrolysis of [prolyl-U-14C]DU-1163 and [prolyl-U-14C]alacepril, respectively. [Prolyl-U-14C]captopril-cysteine was synthesized by condensation of [prolyl-U-14C]captopril with cystine S-monoxide in 55.0% yield.     

The Structure of the Aggregate Form of Bacteriochlorophyll c Showing the Qy Absorption above 740 nm as Determined by the Ring-current Effects on 1H and 13C Nuclei and by 1H–1H Intermolecular NOE Correlations

¹³C-enriched bacteriochlorophyll c (S[I, E] BChl c _F) was suspended in a 1:3 mixture of methylene chloride and carbon tetrachloride to form an aggregate showing the Q_y absorption above 740 nm; changes in the ¹³C chemical shifts were traced when methanol was titrated to dissolve the aggregate, and then, the changes were correlated to the ring-current effects due to the neighboring macrocycles in the aggregate. A pair of aggregate structures has been proposed based on the ring-current effects on both ¹H and ¹³C nuclei; the monomeric units are stacked together to form an inclined column with different sliding directions, in which the y-axis of the molecule is parallel to the long axis of the column. In order to confirm this pair of models, the ring-current effects on the ¹H and ¹³C nuclei were calculated based on both the magnetic-dipole and the loop-current approximations. Further, an application of three-dimensional F1 ¹³C-edited F3 ¹³C-filtered heteronuclear single-quantum correlation-nuclear Overhauser effect spectroscopy to the above aggregate consisting of a 1:1 mixture of ¹³C-labeled and unlabeled BChl c succeeded in detecting selectively the ¹H–¹H intermolecular nuclear Overhauser effect correlations, which established the coexistence of the above pair of stacked structures in the aggregate.     

Preparation of phthalocyanines with eight benzylchalcogeno substituents from 5,6-dibromo-4,7-diethylbenzo[1,2,3]trichalcogenoles

Benzo[1,2,3]trichalcogenoles with two bromine atoms on the benzene ring, 5,6-dibromo-4,7-diethylbenzo[1,2,3]trichalcogenoles (1a) and (1b) (chalcogen: 1a = S; 1b = Se), were first prepared by treating 2,3,5,6-tetrabromo-1,4-diethylbenzene (TBDEB) with elemental sulfur or amorphous selenium in DBU at 140 degrees C (for 1a) and 100 degrees C (for 1b) for 24 h. The structures of 1a and 1b were verified by NMR spectroscopy, mass spectrometry, and elemental analysis. X-ray crystallographic analysis ultimately showed that the substitution reactions of TBDEB proceeded at the two adjacent bromine atoms. To apply 1a and 1b to construction of phthalocyanine derivatives with sulfur or selenium functional groups, 4,5-bis(benzylchalcogeno)-3,6-diethylphthalonitriles (5a) and (5b) as key intermediates were prepared by way of introduction of alkyl groups (2-cyanoethyl or 4-nitrophenethyl groups) on two chalcogen atoms, substitution of two bromine atoms with nitrile groups, and subsequent exchange of alkyl groups with benzyl groups. Compound 5a was treated with lithium in n-pentanol at 100 degrees C for 1 h to produce 2,3,9,10,16,17,23,24-octakis(benzylthio)-1,4,8,11,15,18,22,25-octaethylphthalocyanine (6a). A similar treatment of 5b in n-hexanol at 100 degrees C for 2 h gave phthalocyanine 6b. The structures of 6a and 6b were determined by (1)H NMR spectroscopy and MALDI-TOFMS. X-ray crystallographic analysis of 6a was also performed. The Q-band absorptions (lambda(max)) for 6a and 6b in UV-vis spectra were observed at 755 nm (log epsilon = 5.1) and 757 nm (log epsilon = 5.1), respectively, and their electrochemical properties were verified by cyclic voltammetry in dichloromethane with Ag/AgNO(3) as a reference electrode. Compounds 6a and 6b were further treated with lithium in THF/NH(3) at -78 degrees C and then with dibutyltin dichloride to produce phthalocyanine derivatives 8a and 8b with four dichalcogenastannole rings by way of octachalcogenate phthalocyanines 7a and 7b.     

Nucleoside analogs. I. A synthesis of 1,3-dihydroxy-2-(6-substituted-9-purinyl)cyclohexane

Biologically active 1,3-dihydroxy-2-(6-substituted-9-purinyl)cyclohexanes (VI-X) were prepared by a reaction between trans-2-amino-1,3-cyclohexanediol (I) and 4,6-dichloro-5-amino-pyrimidine (II), followed by cyclization and nucleophilic substitution. Compounds VI and VII showed a weak inhibitory effect against Xanthomonas oryzae, a pathogenic bacteria of leaf blight of rice plant.     

Kinetic resolution of ketone cyanohydrin acetates with a microbial enzyme

Incubation of d1-1-cyano-1-methylalkyl (or alkenyl) acetates (methyl ketone cyanohydrin acetates) with cells of IAM 4682 afforded optically active acetates and the corresponding ketones via asymmetric hydrolysis. Resulting (S)-2-cyano-2-undecyl acetate was converted to the aminofuranone derivative without losing its optical purity.     

The preparation of polysiloxane–vinyl monomer graft and block copolymers

In another paper the radical polymerization of styrene in the presence of various chlorosilanes was investigated, and polystyrenes having chlorosilyl groups as endgroups were obtained. In the present work attempts were made to obtain polysiloxane styrene graft and block copolymers from chlorosilyl polystyrenes. Block copolymers were obtained with dichlorosilane and graft copolymers with tri- and tetrachlorosilanes. In the latter case the insoluble fractions increased, if a suitable stopper, such as butanol or trimethylchlorosilane [(CH₃)₃SiCl], was not used in the condensation reaction. Methyldichlorosilane was used for the preparation of the graft copolymer, because the Si? H bond was more effective than the Si? Cl bond for the chain transfer reaction.     

3-Alkylthio and 3-aminopyrazolo[3,4-D]pyridazines. Ring contraction of pyridazino[4,5-e][1,3,4]thiadiazines via extrusion of sulfur

Reaction of 4-chloro-2-methyl-5-(1-methylhydrazino)-3(2H)-pyridazinone ( 1 ) with carbon disulfide followed by alkylation yielded 2-alkylthio-4H-pyridazino[4,5-e][1,3,4]thiadiazine derivatives 2 . Oxidative cyclization of 5-(4-substituted 1-methylthiosemicarbazido)-3(2H)-pyridazinone derivatives 4 with N-bromosuccinimide also gave 2-substituted amino-4H-pyridazino[4,5-e][1,3,4]thiadiazine derivatives 5 . Heating of 2 and 5 resulted in ring contraction to afford the corresponding pyrazolo[3,4-d]pyridazine derivatives 6, 7 via sulfur extrusion. A possible mechanism for the desulfurization reaction is discussed, comparing with a structural difference between a type of pyridazino[4,5-e][1,3,4]thiadiazine ( 2,5 ) and another one ( 9,11,13,15 ).     

Kinetic resolution of axially chiral 2,2'-dihydroxy-1,1'-biaryls by palladium-catalyzed alcoholysis

Palladium-diamine complexes catalyzed kinetic resolution of axially chiral 2,2'-dihydroxy-1,1'-biaryls by alcoholysis of vinyl ethers. The reaction proceeded with high selectivity for various kinds of biaryls. This process is applicable to not only binaphthols but also biphenols, which have been considered to be difficult for the enantioselective synthesis by known catalytic methods.     

Stereospecific polymerization of methacrylonitrile. V. Formation of the carbonyl in the polymer

The isotactic polymethacrylonitrile prepared by the organometallic catalysts has carbonyl groups in the polymer. Thus, the carbonyl formation during the polymerization by diethylmagnesium was carefully studied by infrared spectrometry. It was found that the imino anion formed by monomolecular termination of the propagating chain end in the cyclization reaction successively attacks the vicinal pendent nitriles in the polymer so as to form the conjugated cyclic imines, which are hydrolyzed to acid amines during the catalyst decomposition with acidic methanol.     

NANOSECOND LASER PHOTOLYSIS OF PHOBORHODOPSIN: FROM Natronobacterium pharaonis APPEARANCE OF KL AND L INTERMEDIATES IN THE PHOTOCYCLE AT ROOM TEMPERATURE

Abstract— Photochemical and subsequent thermal reactions of pharaonis phoborhodopsin (ppR; absorption maximum, 498 nm) from Natronobacrerium pharaonis were investigated by nanosecond laser photolysis at 20°C. The experimental results clearly showed the presence of two intermediates in the photocycle of ppR besides the K, M and O intermediates detected previously. One was formed immediately after the excitation of ppR with a blue pulse (pulse width, 17 ns; wavelength, 460 nm), and the other was formed by the thermal reaction of this species. The new intermediates' absorption maxima were 512 and 488 nm, their extinction coefficients were 0.85- and 0.68-times smaller than that of ppR, and their lifetimes were 990 ns and 32 μs, respectively. The absorption and kinetic characteristics of these intermediates relative to ppR were similar to those of the KL and L intermediates of bacteriorhodopsin (bR). The formation of KL intermediates from both ppR and bR were observed only at room temperatures. On the other hand, the formation of L intermediate of bR was observed at both of room and low temperature, whereas that from ppR only at room temperature. The unique formation of L intermediate of ppR at room temperature is discussed in relation to high thermal stability of K intermediate of ppR.