Oxidation of fatty acids, C8, C16 and suberic acid, in rat renal cortical mitochondria was determined by the standard manometric technique. C8 acid was oxidized more easily than C16 acid. Addition of carnitine promoted the oxidation of palmitate to the level of that of caprylate. C8 and C16 acids were not oxidized by rat renal medullary mitochondria. Suberic acid, intermediate of ω-oxidation of fatty acid, was not oxidized by mitochondria and it was not affected by the addition of carnitine.
Relationship between the structure of diketones and their reactivity in Voges-Proskauer reaction was tested on various α-diketones and their related compounds. Among the compounds tested, only α-diketones involving CH3COCOR were positive and highly sensitive in the O'Meara and Eggleton's method. Glyoxal, methylglyoxal, 3, 4-heptanedione, and 1-phenyl-1, 2-butanedione were positive only to the Eggleton's method and this sensitivity was about 1/27 that of the compounds of CH3COCOR type. Limit of identification was 0.5-30 μg/ml for Eggleton's method and 6.0-90 μg/ml for O'Meara's method. From these results, condensation of free amidino group (H2N-C (=NH)-) and methylketo group (CH3CO-) in α-diketone is considered to be essential for the Voges-Proskauer reaction to take place.
Oxidative phosphorylation (expressed as ADP/O ratio) in liver mitochondria of rats was uncoupled by 2-amino-3-ethoxycarbonyl-6-benzyl-4, 5, 6, 7-tetrahydrothieno [2, 3-c] pyridine (Y-3642) hydrochloride in vitro. The concentration of 20% inhibition of the compound was about 90 μM, which is lower than that of acetylsalicylic acid or Ibufenac, but higher than that of phenylbutazone, Indomethacin, or flufenamic acid. The ADP/O ratio of the mitochondria obtained from rats after oral administration of Y-3642 in a dose of 100 mg/kg was not different from that of untreated control. Y-3642 showed a reverse action on mitochondria swelling ; it promoted at 1000 μM and inhibited the swelling at 500 μM. Activation of mitochondria ATPase in the presence of Y-3642 at a concentration of 100 μM was only 12%, against 227% at 5 μM of flufenamic acid. These results may suggest that Y-3642 produces a functional change in the mitochondria without a structural change and that production or hydrolysis of ATP does not play an important role in the mechanism of anti-inflammatory activity of this compound.
Treatment of diethyl 2-formamido-2-[(2-methyl-5-oxo-1-phenyl-3-pyrazolin-3-yl)-methyl] malonate (IIIa) with formic acid and formaldehyde solution afforded ethyl 1, 5-dimethyl-3-oxo-2-phenyl-1, 2, 4, 5, 6, 7-hexahydro-3H-pyrazolo [4, 3-c] pyridine-6-carboxylate (V), whose structure was confirmed by an alternate synthesis using the Pictet-Spengler reaction. Additionally, some analogs of V containing alkylcarboxamide groups at the 6-position were prepared.
The Hofmann degradation of quaternary ammonium compounds was examined with 2-alkyl-, 2, 4-dialkyl-, and 2, 4, 6-trialkyl-piperidinium iodides. Thermal decompotion of 2-pentylpiperidinium hydroxide (IV6) produced 5-dimethylamino-1-decene (B) (47%), 1-dimethylamino-4-decene (C) (38%), and 1-dimethylamino-5-decene (D) (15%) (Table II). Elimination generally occurs preferentially in the piperidine ring, rather than in the 2-alkyl chain, except when the alkyl is a methyl group. This result may be interpreted as being due to the steric effect in the planer trans transition state during formation of olefins from quaternary bases.
Application of acetophenone to 2-substituted quinoxaline 4-oxides (I) in the presence of sodium amide in dehyd. benzene, under ice cooling, afforded 2-substituted 2-phenacyl-quinoxaline 4-oxides (II) in a fairly good yield. The compounds submitted to this reaction were 2-ethyl (Ia), 2-isopropy (Ib), 2-tert-butyl (Ic), 2-ethoxy (If), 2-benzyloxy (Ig), and 1-methyl-1, 2-dihydro-2-oxo (Ih), derivatives, which respectively afforded 3-ethyl (IIa), 3-isopropyl (IIb), 3-tert-butyl (IIc), 3-phenyl (IId), 3-methoxy (IIe), 3-ethoxy (IIf), 3-benzyloxy (IIg), and 4-methyl-2-phenacyl-3, 4-dihydro-3-oxo (IIh), derivatives.
Since the reaction of thioanilide-type compounds and aromatic primary amines easily affords amidine compounds by dehydrosulfuration, reaction between 2-thiopicoline anilides (I) and ortho-substituted bifunctional compounds (o-phenylenediamine, o-amino-phenol) was carried out and it was found that cyclization occurred by liberation of hydrogen sulfide and anilide group, resulting in the formation of imidazole and oxazole rings. Optimal conditions for cyclization by this kind of reaction were examined from reaction temperature, time and solvents used. Liberation of the anilide group from thioanilides suggested the effect of a substituent group in the anilide on the rate of formation of cyclization. Therefore, some 2-thiopicoline anilides were prepared having p-methyl, p-methoxy, p-ethoxy, p-ethoxycarbonyl, o-methyl, o-methoxy, and m-methyl as a substituent. It was thereby found that electron-donating groups tended to decrease the formation rate, both in the formation of 2-(2-pyridyl) benzimidazoles and 2-(2-pyridyl) benzoxazoles.
Thermal decomposition of sec-alkyldimethylamine methohydroxide (VIII, XII) was examined by pyrolysis-gas chromatographic method, with respect to two reactions, β-elimination and substitution at N-methyl groups. Its result, when compared with known results for methohydroxides of alkyldimethylamines, illustrated the marked inhibitory effect of an alkyl group attached to the α-carbon atom on β-elimination, relative to substitution. Branching of a sec-alkyl group at the γ-carbon atom farther decreases the conversion of to an olefin. The relative ammount of isomeric olefins formed in the thermal decomposition of unsymmetrical sec-alkyl quaternary ammonium compounds was also determined.
Reaction of primary enamines, such as 3-aminocrotononitrile (IIIa), β-aminocinnamonitrile (IIIb), 4-amino-3-penten-2-one (IIIc), and ethyl β-aminocinnamate (IIId), with ketene gives results in acylation of their enamine-carbon to give C-acetates (Va, b) or C, N-diacetates (VIc, d). Acetylation of III (a to d) with acetic anhydride gives their N-acetates (IVa-d) whose reaction with ketene does not afford C, N-diacetates (VI). On the other hand, III (a to d) reacts with diketene and their enamine-carbon and-nitrogen are both acylated, giving 2, 3-disubstituted 6-methyl-4-pyridone (VIIa-d), N-acetoacetate (IXa, b), and 2, 6-dimethyl-4-oxopyran-3-carboxamide derivatives (Xa, b). Similar results were also obtained with other enamines such as ethyl 3-aminocrotonate (IIIe), 3-amino-2-cyclohexen-1-one (IIIf), and 3-amino-5, 5-dimethylcyclohexen-1-one (IIIg).
Complexes of 5'-guanylic acid with various metals such as copper, zinc, lead, cadmium, nickel, cobalt, and manganese were isolated as a crystalline precipitate from the solution of pH 3.5-6.5. Metal to ligand ratio was found to be 1 : 1 in all cases. The infrared spectra of these complexes were compared with those of sodium, potassium, calcium, and barium salts. In these complexes, the coordination with phosphate group was confimed from the infrared absorption in the region of 988-1000 cm-1. The coordination with guanine ring moiety was also assumed from the observation on the band of C=O stretching vibration.
A red pigment was formed in the incubation system which contained, Mn2+, hemoglobin, and 3-hydroxyanthranilic acid. This pigment was identified as cinnabarinic acid by comparing its properties with a synthetic sample. This reaction had an optimum pH at 7.2 and an initial lag-phase. Heavy metal ions and reducring agents like Ag+, Hg2+, Cu2+, glutathione, cysteine, and ascorbic acid inhibited the pigment formation. These characteristics were similar to those of the enzymatic formation of cinnabarinic acid catalyzed by cinnabarinic acid synthase.
In the survey of the root constituents of a valerian indigenous to Mt. Ibuki, central Honshu, a number of sesquiterpenoids have been isolated or detected. This valerian is characterized by containing sesquiterpenoids of the valerane skeleton (in particular, valeranone, cryptofauronol, and fauronyl acetate) in large quantities, but those of the kessane skeleton in minute amounts.
In order to examine the relationship between the structure and activity in progestational streoids, 17α-acetoxyprogesterone derivatives having 7α-alkylthio and/or 7α-arylthio group were synthesized. Among these compounds, 7α-methylthio derivative (IIb) showed the most potent progestational activity.
The structure of 2-phenyl-3-cyano-6-methyl-4-pyridinol (III), proposed by von Meyer in 1908 for the crystalline product of mp 244° obtained by the reaction of β-aminocinnamonitrile (I) with ethyl acetoacetate, is pointed out as an error and the correct structure for it proposed as 4-methyl-5-cyano-6-phenyl-2-pyridinone (IV). The compound corresponding to III is obtained by the reaction of I with diketene.
From the fresh leaves of Formosan Melicope confusa (MERR). LIU, skimmianine (II), kokusaginine (IV), and a new furoquinoline-type alkaloid, confusameline, were isolated. The new alkaloid, confusameline, occurs as light brownish needles, mp 239-240°, and its methylation with diazomethane gives evolitrine (XIV). By the comparison of signal positions of methoxyl groups in the nuclear magnetic resonance (NMR) spectrum of the O-ethyl compound (XV), obtained by ethylation with diazoethane, and the NMR spectra of several known furoquinoline-type alkaloids which have already been reported (Table I), the structure of confusameline was proposed as formula XIII.