A convenient and practical synthesis of 2-cyclopentenone has been developed.

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The dotetracontapeptide corresponding to the revised amino acid sequence of porcine GIP (glucose-dependent insulinotropic polypeptide; originally named gastric inhibitory polypeptide) was synthesized by assembling eight peptide fragments of established purity, followed by thioanisole-mediated deprotection with trifluoromethanesulfonic acid in trifluoroacetic acid. The cycloheptyl esters of aspartic acid and glutamic acid were employed to suppress base-catalyzed side reactions. When tested in dogs, the synthetic peptide produced a significant increase of immunoreactive insulin in blood under background infusion of glucose.

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The occurrence of a new bufotoxin, hellebritoxin, together with known five bufogenins and three bufotoxins in the skin of the green toad, Bufo viridis LAUR., is reported. The structures were elucidated by degradative means and/or direct comparison with authentic samples. These bufadienolides were assayed for inhibitory activity towards guinea pig heart Na⁺, K⁺ -adenosine triphosphatase.

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The (E)-isomer (11) of FK027 was synthesized by two methods. The effect of the configuration of the oxime in the 7-acyl side chain of FK027 (1) on the antimicrobial activity and oral absorbability in rats was investigated. Both FK027 (1) and its (E)-isomer (11) showed appreciable oral absorbability regardless of the configuration of the oxime.

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Cerevisterol (1) and a new acetylenic compound, 4, 6-decadiyne-1, 3, 8-triol (2) were isolated and characterized from a hallucinogenic mushroom, Gymnopilus spectabilis (FR.) A. H. SMITH, along with ergosterol, ergosteryl peroxide and choline.Psychoactive compounds such as psilocybin and related compounds have not been detected in our collections of this mushroom, though some psilocybin has been found in several other Japanese mushrooms.

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Highly sensitive electrochemical mathods for the assays of glucose, uric acid and total cholesterol in serum were established by using peroxidase adsorbed on a carbon electrode.Glucose, uric acid and cholesterol were oxidized by glucose oxidase uricase and cholesterol oxidae, respectively, to give a hydrogen peroxide, which was measured by means of a hydrogen peroxide sensor using peroxidase adsorbed on a carbon electrode. Each method required 5 μl of serum, and the detection limits of glucose, uric acid and total cholesterol were 0.10 μg (0.555 nmol), 0.05 μg (0.295 nmol), and 0.25 μg (0.650 nmol) per assay tube, respectively.

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The effects of the shape of the reaction vessel, the sample volume and the volume and speed of the reagent injection on the reproducibility of the chemiluminescence (CL) analyses were investigated with a laboratory-built automated injection device and a computer system. The sutitable selections of the vessel diameter as well as the injection volume are shown to be necessary for the precise measurements of samples of given volume. Under the optimal mixing conditions, the choice of signal processing such as peak height measurements or fixed-time integration did not affect the reproducibility and any of the methods used could give accurate CL values. These principles for the precise measurement represent useful guides for luminometer designing and experiments for rapid, precise analyses.

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The kinetics and mechanism of the degradation of chlorphenesin carbamate (α-CPC) in various strongly acidic aqueous solutions were studied at 40 to 60°C.The degradation of α-CPC obeyed pseudo first-order kinetics. The rate law of the degradatioin could be explained in terms of specific acid-catalyzed hydrolysis. From the analysis of the Arrhenius plot of the degradation, which was linear, the apparent activation energy and the apparent entropy at 50°C of the degradation reaction were calculated to be 21.8 kcal·mol^-1 and -21.3 cal·deg^-1·mol^-1, respectively.Chlorphenesin was detected as the acidic degradation product of α-CPC. The degradation mechanism in a strongly acidic aqueous solution was different from that in the strongly alkaline aqueous solution obtained previously and was shown to involve the removal of the carbamoyl group by hydrogen ion catalysis without isomerization.

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Formation of N-nitrosamines from nitrite and secondary amines in acidic solutions was affected by inorganic and organic salts such as chloride, succinate, citrate and tartrate. Formation of N-nitrosodimethylamine at pH 5 was inhibited more effectively than pH 3. The dissociation constant of nitrous acid-nitrite in the solution was decreased by addition of these salts. The salts influenced the nitrous acid nitrite equilibrium to inhibit N-nitrosation of secondary amines.

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The Diels-Alder reactions of (1E__-), (3E__-)-2-methyl-1-trimethylsilyloxy-1, 3-pentadiene with methyl acrylate and methyl (2E__-)-pentenoate were investigated. One of the adducts was used to synthesize some multistriatins.

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A method is proposed to estimate the hydrophobic interaction energy for the binding of a ligand to an enzyme. The hydrophobic energy for the association of methotrexate and dihydrofolate reductase was estimated by this method. Compensations were found between the hydrophobic and the electrostatic energies for the constituent functional groups in methotrexate. The association may be unfavorable from the viewpoint of hydrophobicity; it may be electrostatically driven.

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The bis-derivatives (4-6) of 8-hydroxyquinoline, which, like tropolones, readily form a chelate, were synthesized and found to be actively antitumorous in tests of survival using P388 mice. 4 was almost as potent as bistropolone (2a).

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A reaction of formaldehyde with hydralazine (HP) under weakly acidic conditions resulted in a rapid, almost constant yield of s-triazolo[3, 4-a]-phthalazine (Tri-P) which could be determined directly and sensitively by high-performance liquid chromatography without extraction. This procedure is believed to be a useful method for determining formaldehyde in aqueous samples.

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A radioimmunoassay (RIA) specific for rat T-kiniogen (T-kgn) has been developed using ¹²⁵I-labeled purified rat T-kgn and anti T-kgn antiserum developed in rabbits. By this RIA 0.5-16 ng of T-kgn can be measured using a linear calibration curve. Cross-reactivities of purified rat high-molecular-weight kininogen and low-molecular-weight kininogen were about 0.29 and 0.15%. By this assay the level of T-kgn in normal rat plasma was found to be about 0.3 mg/ml, and it increased 10 to 20-fold when rats were treated with turpentine.

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The protected carboxamide function of N^α, N^ca-di-tert-butyloxycarbonyl-ω-carbamoyl-α-amino acids worked well with nucleophilic reagents. Applying this novel reactivity, we developed an efficient synthetic route to N^α-tert-butyloxycarbonylhomoglutamic acid and its derivatives, including N^α-tert-butyloxycarbonylhomoglutamic acid δ-benzyl ester, from N^α, N^ca-di-tert-butyloxycarbonylhomoglutamine.

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The diethylhydrogensilyl-cyclic diethylsilylene (DEHS-DES) derivative of thromboxane B₂ (TXB₂) methyl ester-methyloxime was prepared by treating with diazomethane, O-methylhydroxylamine-HCl and then with N, O-bis(diethylhydrogensilyl)trifluoroacetamide (DEHS-BSTFA). The gas chromatogram of the reaction product showed a well-resolved doublet using a 5% phenylmethylsilicon cross-linked fused silica capillary column, corresponding to the syn- and anti-isomers. In their mass spectra, these components showed an ion of at 269 as a base or prominent peak. This ion and many other characteristic ions reflect the TXB₂ system with moderate intensity. The ion at m/z 269 consisted of a fragment of the DES ring moiety and the α-side chain. The mass spectrum of the second eluting component was considerably more complex than that of the first. Almost all of the fragment ions in the mass spectrum of the first eluting component were also observed in that of the second component. When gas chromatography/high resolution-selected ion monitoring (GC/HR-SIM) was carried out at a resolutioin of 8000 to monitor the ion of m/z 269. 1753, specific for the structural integrity of TXB₂, the selected ion recording (SIR) showed a well-shaped doublet with signal to noise ratio (S/N) of greater than 300 after an injection of 25 pg of the derivative.

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A number of lignans, including those isolated from Arctium lappa (Compositae), were subjected to Ca²⁺ antagonist assay. The most potent activity occurred in trachelogenin, the calculated Ic50 and pA₂ of which were 1.1×10^-6 M and 6.60 respectively. Tranchelogenin had a potent and long-lasting antihypertensive effect on spontaneously hypertensive rats.

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(±)-Eperuane-8β, 15-diol (5__∼) and (±)-labdane-8α, 15-diol (6__∼), diastereomeric diterpenes to each other, were synthesized stereoselectively, via the same intermediate lactone (7__∼) starting from a known racemic tricyclic compound (8__∼).

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A silver/silver chloride (Ag/AgCl) electrode coated with a tri-n-dodecylamine/poly(vinyl chloride) composite membrane was used to make potentiometric enzyme sensors. When the pH-sensitive membrane-coated Ag/AgCl electrode was further coated with a urease or penicillinase membrane, it responded potentiometrically to urea and penicillin. The performance of the enzyme sensors was comparable to conventional enzyme sensors.

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The cyclooxygenase products of rabbit platelets stimulatd with arachidonic acid were measured by HPLC. Prostaglandins and thromboxane were extracted, derivatized with 9-anthryldiazomethane, and then loaded on an ODS-column. The fluorescence of the eluate was monitored. Thromboxane B₂ was a major product, which returned to the control level in the presence of indomethacin or the thromboxane synthetase inhibitor OKY-046. Pretreatment with OKY-046 shifted the cyclooxygenase products to increased levels of PGE₂, PGD₂ and PGF_2α.

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A new and simple synthesis of (±)-emetine uses α, β-unsaturated lactams (4__∼b__∼), (4__∼c__∼), and (4__∼e__∼) as new Michael acceptors.

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The late stage of patulin biosynthesis was studied using cell-free preparation of Penicillium patulum NRRL 2159A. The substrate for the ring cleavage reaction was established to be gentisyl alcohol, which was converted into patulin by a microsomal enzyme(s). Incubation of [1'-¹⁴C, ³H₂]-gentisyl alcohol with the microsomal preparation revealed that one of the carbinol protons of this substrate is retained in patulin. This answers the long-standing question why the side chain protons of aromatic intermediates are not incorporated into patulin in feeding experiments.

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