Chemistry and biological activities of macrocyclic polyamines have been studied to disclose (1) special features of mode of their proton uptake ; (2) uptake of biological polyanions (such as TCA cycle polycarboxylates, phosphate, ATP and carbonate) and of catechols (such as dopa and dopamine) ; (3) inclusion of soft metal ions (e.g. Cu2+) ; (4) selective uptake of hard metal ions (e.g. Mg2+) ; (5) peptide-like functions to stabilize unusual oxidation state of metal ions (e.g. Cu3+, Ni3+) ; (6) superoxide dismutase-like activities by macrocyclic polyamine complexes ; (7) biogenic polyamine-like activities ; and (8) heme-like O2-uptake and activation functions by metal complexes. These newly discovered properties will prove to be useful for the future development of entirely new type of medicines, chemicals, catalysts and so on.
Usual photochemical reactions occur from either directly light-absorbed molecules (direct photoreaction) or exothermic energy transfered molecules (sensitized photoreaction). Recently, many new examples of the third photoreaction [electron transfer (ET) photoreaction] have been published. The ET photoreaction involving the excited state electron transfer from an electron donating compound (D) to an electron accepting compound (A) normally proceeds via an exciplex (excited state charge transfer complex) or a solvated radical ion pair (D+.·A-.), and is quite important because it has opened the possibility of "formal endothermic sensitization." Usual ET photoreactions can be classified into four types concerning product (P) formation ; type 1 (D+A→P), type 2 (D+A→P+D), type 3 (D+A→P+A), and type 4 [(D…A]CT→P]. This article explains the above four types of ET photoreactions using examples mainly developed in this laboratory ; photo-Friedel-Crafts reaction, photocyclization of imide, photohydrolysis of sulfonamide, photocleavage of water, oxidative cleavage of aromatic ring, and strained cage formation as a light energy conversion model.
Upon examination of the precipitate-formation in the solution of geraniin, punicalin or tannic acid JP, mixed with that of Cd2+, Cr6+, Cu2+, Fe3+, Hg2+, Mn2+, Pb2+, or Zn2+, at pH 5.4, the amount of precipitate generally increased with an increase in concentration of tannin, in the experiments with lower tannin-concentration. However, the amount of precipitate decreased with an increase in concentration of punicalin or tannic acid JP, of 1×10-3-5×10-3M, in several experiments. The precipitates once formed in these experiments were also solubilized upon further increase of the tannin concentration. Simultaneously, the amount of heavy metal in the supernatant liquor, and also the ratio of tannin to heavy metal in the precipitate increased. Extensive reduction of Cr6+, Fe3+ and Cu2+, along with the complex formation, occurred in the presence of tannins (geraniin, punicalagin and tannic acid JP) and (-)-epigallocatechin gallate. Each metal ion was determined by colorimetry, and the formation of soluble complex was exhibited by paper electrophoresis. These results indicate that the toxicity of metal ions could be reduced in the presence of tannins and polyphenols.
The synthesis of 2-methyl-1-phenyl-6, 7-dihydro-1H, 5H-pyrazolo [5, 1-b] [1, 3] oxazin-8-ium bromide (VII) and its reactions with some nucleophilic reagents were carried out : The reaction of 3-hydroxy-5-methyl-1-phenylpyrazole (IV) with trimethylene bromide in dimethylformamide (DMF) in the presence of potassium carbonate gave VII (86%) and 1, 3-bis (5-methyl-1-phenyl-3-pyrazolyloxy) propane (VIII) (6%). Treatment of VII with 5% aqueous sodium hydroxide solution or sodium hydrosulfide in DMF gave 1-(3-hydroxypropyl)-3-methyl-2-phenyl-3-pyrazolin-5-one (VI) (80%) or 1-(3-hydroxypropyl)-3-methyl-2-phenyl-3-pyrazoline-5-thione (IX) (55%). However, the reaction of VII with sodium p-nitrophenolate or sodium diethyldithiocarbamate gave 3-methyl-1-[3-(p-nitrophenoxy) propyl]-2-phenyl-3-pyrazolin-5-one (X) (74%) or 3-(3-methyl-5-oxo-2-phenyl-3-pyrazolin-1-yl) propyl N, N-diethyldithiocarbamate (XI) (72%).
N-Substituted 6-amino-3-oxo-1-hexanoate (11b, c, 4a-c), which were obtained from γ-amino-n-butyric acid (GABA) and γ-amino-β-hydroxy-n-butyric acid (GABOB), were treated with strong acid to give 2-(2-pyrrolidinylidene) acetate derivatives (12b, c, 15a-c) and 2-pyrroleacetic acid derivatives (8a, b). Though the conversion of 2-[1-(3-chloro-1, 4-dioxo-2-naphthyl) pyrrole] acetic acid derivatives (8a, 15c) to methyl 3H-pyrrolo [1, 2-a] benzo [f] indole-5, 10-dione-11-carboxylate (9) was not successful, its convertible precursor 7b was synthesized via azocinone derivative (6a), starting from methyl 6-(3-chloro-1, 4-dioxo-2-naphthyl) amino-3-oxo-5-(2-tetrahydropyranyloxy)-1-hexanoate (4a).
It is elucidated that aucubigenin (2) is an active substance for the antimicrobial activity of the enzymatic hydrolysis product of aucubin (1). Some other iridoid aglycones also showed similar antimicrobial activity.
For the purpose of evaluating the quality of crude drugs derived from animal gall, free, glycine- and taurine-conjugated bile acids were directly analysed by HPLC equipped with a 3α-hydroxysteroid dehydrogenase-immobilized column. Various commercially available galls showed characteristic bile acid composition depending on their sources (snakes, frogs, chickens, pigs, wild boars, cattle and bears), and could be chemically distinguished each other. One of dried snake galls sold in the market was a counterfeit derived from frog gall. Furthermore, some dried bear galls seem likely to be counterfeits derived from cattle gall or mixed with pig and/or cattle gall in comparison with the gall definitely derived from Sus scrofa domesticus BRISSON, Bos taurus domesticus GMELIN, Selenarctos thibetanus japonicus SCHLEGEL and Ursus acros L.
Lipofuscin-like fluorescent substance was obtained from the reaction of β-phenylethylamine and n-hexanal, which is one of the secondary products of autoxidized methyl linoleate and it was separated by high performance liquid chromatography and thin layer chromatography. This fluorescent substance showed excitation maxima 366 nm and emission maxima 428 nm. The addition of unsaturated aldehyde, that is, 2-hexenal, crotonaldehyde or 2-n-butyl-2-octenal derived from aldol condensation of n-hexanal in the reaction system increased significantly the formation of fluorescent substance. However, the main product in this reaction system was a shiff base compound from β-phenylethylamine and 2-n-butyl-2-octenal, but was not fluorescent substance. On the other hand, the fluorescent substance obtained from the reaction of malondialdehyde and β-phenylethylamine was 1, 4-dihydropyridine derivative, three molar malondialdehyde condensed with one molar β-phenylethylamine. These results suggested that lipofuscin-like fluorescent substance would be formed from the reaction of various amino compounds and dialdehyde compounds derived from"michael reaction"of saturated aldehyde compounds and unsaturated aldehyde compounds.
The assay for potency was carried out by use of 35 kinds of sulfur containing compounds in order to investigate useful protective drugs for the relief of skin injury caused by irradiation and to elucidate the relationship between their chemical structures and potency manifestation. The protective potency was determined after the irradiation of 1200 R on mice by use of 30 kVp of soft X-ray. In derivatives such as cysteamine, cysteine, thiourea, and isothiourea, a strong protective potency was observed and this potency was enhanced in compounds on which SH-groups are released or apt to be released from a chemical structural point of view. In dithiocarbamates, protective potency was also detected.
The metabolic fate of 9, 3"-diacetylmidecamycin (MOM) was studied in several animal species and in man. The metabolites were isolated from the urine, bile, and incubation mixture of rat liver homogenate and characterized by mass and nuclear magnetic resonance spectra. The first step in the metabolic pathway of MOM has been shown to be a hydrolysis of an ester moiety in the 4"position, followed by spontaneous migration of an acyl group from 3"to 4"position, thereby forming 9, 4"-diacetylmidecamycin (Mb-1). The next step is a deacylation of 4"-acetyl group of Mb-1, to give 9-acetyl-4"-depropionylmidecamycin (Mb-2) ; Mb-2 is then hydroxylated to Mb-3 and Mb-5 (the diastereoisomers which differ only in the stereochemistry at C-14). In animals, the main metabolic route has been demonstrated to be as follows : MOM→Mb-1→Mb-2→Mb-3 and Mb-5. The other metabolic pathway of Mb-1 is a deacylation of 9-acetyl group to give 4"-acetyl-4"depropionylmidecamycin (Mb-12). Mb-12 is then hydroxylated at C-14 and/or deacetylated at 4". This latter metabolism has been shown to be a main course in man. In rat, about 14 and 28% as metabolites of the administered drug, respectively, have been shown to be excreted in the urine and bile. The parent antibiotic was detected neither in the urine, bile, nor in blood. Though about 1/3 of the total metabolites was detected as conjugated forms in the rat bile, the conjugates were excreted in a quite small amount (1-2% of the total urinary metabolites), in the case of the rat urine.
The contents of 6-keto-prostaglandin F1α (6KF1α) and thromboxane B2 (TXB2) in mouse peritoneal macrophages were determined by radioimmunoassay. When indomethacin at a final concentration of 0.1 mM was added at each stage in the preparation of macrophage samples, i.e. (I) before incubation of peritoneal exudate cells in glass dishes to prepare macrophage monolayers, (II) before harvest of macrophages from the glass surfaces, (III) before sonication of macrophage suspensions, and (IV) before centrifugation of sonicated macrophage solutions, large differences were detected in the contents of 6KF1α and TXB2 at each stage. These results suggested that physical stimulation during the preparation of samples resulted in increases of 6KF1α and TXB2 production by macrophages.