Nineteen benzo[α]quinolizidine alkaloids (1-19) isolated so far from Alangium plants can be classified into four types (I-IV) according to their chemical structures. Studies on racemic and chiral syntheses of these I-IV-type alkaloids are reviewed with particular emphasis on the strategies and tactics for the syntheses employed by the author. It has been found that racemic syntheses of all of these types of alkaloids are possible through the "lactim ether route" or the "3-acetylpyridine route"; and chiral syntheses, through the "cincholoipon-incorporating route" or the "chiral lactim ether route". As a result of such total syntheses, the structures and absolute configurations of four II-type, two III- type, and two IV-type Alangium alkaloids have been established. Extensions of the "chiral lactim ether route" to the syntheses of the Ochrosia alkaloid (-)-ochropposinine [ (-)-93g], the Neisosperma alkaloid (-)-ochromianine [(-)-97], and the Ophiorrhiza alkaloid (-)-ophiorrhizine [(-)-98] have unequivocally established the absolute stereochemistries of these three indolo[2, 3-α]-quinolizidine alkaloids.
The studies on the syntheses and reactions of purines and their nucleosides, carried out by the present author's group for these 34 years, are reviewed with particular emphasis on the employed synthetic strategies and tactics. Among the studies included in this review are as follows : ring-opening and recyclization of the adenine ring utilizing an N(1)-alkoxy group; kinetic studies of the Dimroth rearrangement and related reactions in the adenine series; syntheses and reactions of new Nx, Ny-disubstituted adenines and of new Nx-substituted adenosines; syntheses, structure determinations, and structure-activity relationships of new natural cytokinins; syntheses and reactions of new marine 8-oxopurines; syntheses, reactions, and biological activities of the N(7)-oxides of guanine, hypoxanthine, adenine, 6-mercaptopurine, and 6-methylthiopurine.
Immunoglobulin G (IgG) is an important protein in humoral immunity. After IgG binds to the specific foreign antigen, IgG-antigen complexes are eliminated either by making it easier for a phagocytic cell to ingest them or by activating a complement system. We found that the carboxyamidemethylated subfragments obtained from human serum IgG by reduction and alkylation of its interchain disulfide bonds, have anti-ulcerogenic, anti-inflammatory and antiallergic activities, while no activity was recognized in the original IgG. On the other hand, some saturated and unsaturated fatty acids generally existing in microorganisms were found to have anti-inflammatory and anti-ulcerogenic activities. As the application of these researches, we synthesized hybrid compounds from sulfur-containing amines and fatty acids to make a lead compound for developing a new medicine. In this review, the experimental process will be discussed.
The antihypertensive effect of tea-leaf saponin (the saponin mixture isolated from leaves of Camellia sinensis var. sinensis) was examined in spontaneously hypertensive rats (SHR). Tea-leaf saponin reduced a time-dependent increase in blood pressure dose-dependently when it was administered orally to young SHR (7 weeks old) for 5 d. Oral administration of tea-leaf saponin to elder SHR (15 weeks old) for 5 d decreased the mean blood pressure by 29.2 mmHg at the dose of 100 mg/kg compared to the control group. Single administration of tea-leaf saponin at 50mg/kg, p.o. showed a long-lasting hypotensive effect and this effect was as potent as that of enalapril maleate at the dose of 3 mg/kg, p.o. Tea-leaf saponin inhibited angiotensin I-induced contraction of the isolated guinea pig ileum in a dose dependent manner but little depressed angiotensin II-induced contraction. On the other hand, in in vitro experiment using a synthetic peptide as a substrate, tea-leaf saponin showed almost no inhibitory activity against the angiotensin I converting enzyme (ACE) (IC50>10 mg/ml).
A number of sulfur-containing amide-carboxylic acid derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in only two series, that is, sulfoxide-carboxylic acid derivatives (9) and sulfone-carboxylic acid derivatives (10). As the most preferred compound, 5-(3, 4-dichlorophenylsulfonyl)-4-(N, N-dipentylcarbamoyl)pentanoic acid (10n) was selected.
We previously suggested that the colouration (browning) of Toki-shakuyaku-san extract granules (TJ-23) was related to the Maillard reaction under heat-stress storage. In this study, we investigate the production of browning high-molecular compounds and discuss the relationships among the respective contents of these compounds, amino acids and reducing sugars and the colouration (ΔE*(ab)) of TJ-23 under heat-stress conditions. As a result of the investigation, it was found that peaks corresponding to the high-molecular compounds were separated from the heat-stressed samples of TJ-23 at each molecular weight of about 5000, 10000, 230000 and 3000000, and especially the latter two peaks increased in areas up to about 11 times and 4 times at 60°C from 10 through 90d respectively. At the same time, it was confirmed that the contents of amino acids and reducing sugars decreased with an increase in storage temperature at 10d. Furthermore, it has become apparent that the content of high molecular compounds was correlated with colour differences (ΔE*(ab)) of heat-stressed TJ-23, and then those compounds were related to the decreases of glucose and amino acids. From these results, we confirmed that the browning of Kampo medicines extract granules might proceed partially by Maillard reaction under higher temperature and/or longer time conditions.