This review deals with recent progress of the synthetic studies on monoterpenoid indole alkaloids which have been known to be biogenetically derived from common key intermediates, secologanin and tryptamine. Concerning construction of the ring systems of yohimbane and corynantheine-heteroyohimbine alkaloids, the synthetic strategies and tactics reported in recent ten years are discussed.

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In order to clarify the biochemical functions of antitumor antibiotics bleomycins, model ligands corresponding to the metal binding site of bleomycin have been designed, synthesized and characterized. Metal binding properties of these models were found to be virtually identical to those of bleomycin. It was demonstrated that the 4-aminopyrimidine nucleus and the disaccharide moiety of bleomycin could be replaced by a 4-methoxypyridine ring and a tert-butyl group, respectively, and such model compound showed an efficient dioxygen activating capability comparable to that of bleomycin. This model ligand was coupled with the deoxyribonucleic acid (DNA) affinity moiety of bleomycin to give a man-designed bleomycin, which showed potent DNA cleaving activity in vitro.

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Tryptophan, an indispensable amino acid, is not only the constituent of protein, but also replaced into biologically active molecules such as indole-3-acetic acid and serotonin. In order to clarify the physiological function of these indole compounds, their interaction modes, especially the indole ring which they contain commonly, with biomolecules must be known at atomic level. The present review has been discussed on the interaction of indole ring with vitamin B coenzymes (pyridine, flavin, thiamine, and pyridoxal) and with nucleic acid bases (adenine, guanine, and pyrimidine), based on X-ray crystal structural and solution spectroscopic studies. A significant characteristic commonly observed in the interactions of indole compounds with pyridine, flavin, and thiamin coenzymes is the prominent π-π stacking formation including partial charge-transfer, and this suggests that in addition to the importance of tryptophan residue for enzyme-apoenzyme interaction, their catalytic reactions are accelerated by the partial, π-electron transfer from indole ring. On the other hand, the conformational analysis of tryptophan-pyridoxal Schiff base has shown a reasonable metabolic pathway according to Dunathn's hypothesis. In contrast with neutral adenine and guanine bases, their protonated or methylated ones are strongly bound with indole ring through prominent π-π stacking interactions, providing a clue for understanding the selective recognition mechanism of nucleic acid bases by tryptophan. Indole ring also binds with pyrimidine bases by stacking interactions. The specific π-π stacking formation commonly observed in the interactions of indole ring with these important biomolecules, which is stabilized by strong molecular orbital couplings between respective aromatic rings in addition to electrostatic and/or dipole-dipole ones, is served for diverse biological reactions.

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Inhibitory effects of about twenty five tannins and their related compounds on autoxidation of methyl linoleate were studied by kinetic, static and in situ electron spin resonance (ESR) measurements. Almost all tannins examined showed nearly as large inhibitory effects as that of α-tocopherol. Polyphenols with low molecular weight, such as gallic acid, pyrogallol etc., showed a minor inhibitory effect. The rate of inhibition by tannins was represented as follows : V_inh=-d[O₂]/dt=k[RH]^1.2[AIBN]^0.6[Tannin]^-0.4 This kinetics was reasonably explained by a proposed radical scavenging mechanism by tannins, where the tannins acted as radical scavenger of chain carrying peroxy radicals. The inhibitory activities of tannins were dependent on both the type of phenolic groups and their numbers in the molecules. The scavenging activity of the phenolic group was in the order of hexahydroxydiphenoyl (HHDP) group > galloyl group. That is, the tannins with many HHDP groups in the molecule exhibited larger inhibitory effects compared with tannins with galloyl groups only. In situ ESR detection of tannin radicals under the inhibitory conditions was carried out, and transient ESR signals of tannin radicals were observed in good resolution. These signals coincided well with those obtained by air-oxidation of tannins in aqueous alkaline DMSO solution carried out in separate ESR measurements. Thus, the radical scavenging mechanism by tannins was confirmed to be operative in our inhibited peroxidation systems.

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Three new glucuronide-saponins, named kaikasaponin I (7), kaikasaponin II (8), and kaikasaponin III (9), were isolated from Sophorae Flos, the buds of Sophora japonica L. (Leguminosae), together with five known glucuronide-saponins soyasaponin I (6), soyasaponin III (4), azukisaponin I (2), azukisaponin II (3), and azukisaponin V (5). By use of the photochemical degradation method, which is one of selective cleavage-methods for the glucuronide linkage in glucuronide-saponins, and on the basis of chemical and spectral evidence, the structures of kaikasaponins I, II, and III have been determined as 3-O-[β-D-galactopyranosyl-(1→2)-β-D-glucuronopyranosyl]sophoradiol (7), 3-O-[α-L-rhamnopyranosyl-(l→2)-β-D-glucopyranosyl-(l→2)-β-D-glucuronopyranosyl]sophoradiol (8), and 3-O-[α-L-rhamnopyranosyl-(1→2)-β-D-galactopyranosyl-(1→2)-β-D-glucuronopyranosyl]sophoradiol (9), respectively. In the course of ¹³C nuclear magnetic resonance spectral analysis of these kaikasaponins, it has been noticed that some chemical shifts of carbohydrate carbons close to the sapogenol are affected by the presence of a hydroxyl group in the sapogenol nearby the glucuronide linkage.

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From the aerial part of North American alfalfa, Medicago sativa L. (Leguminosae), a new glucuronide-saponin named dehydrosoyasaponin I (7) and two glycero-glycolipids (8, 9) were isolated together with three known glucuronide-saponins, soyasaponin I (6), azukisaponin II (4), and azukisaponin V (5). the structure of dehydrosoyasaponin I has been determined as 3-O-[α-L-rhamnopyranosyl-(1→2)-β-D-galactopyranosyl-(1→2)-β-D-glucuronopyranosyl]soyasapogenol E (7) from the chemical and spectral evidence. Two glycero-glycolipids have been elucidated respectively as 1-O-β-D-galactopyranosyl-2, 3-di-O-acyl-D-glycerol, in which the acyl group comprises linolenoyl (90%), linoleoyl (8%), and palmitoyl (2%) residues (8), and 1-O-[α-D-galactopyranosyl-(l→6)-β-D-galactopyranosyl]-2, 3-di-O-acyl-D-glycerol, in which the acyl group comprises linolenoyl (85%), linoleoyl (5%), palmitoyl (5%), oleoyl (3%), and stearoyl (2%) residues (9). On the structure elucidation of 9, the lead-tetraacetate degradation method, which is one of selective cleavage methods for the glucuronide linkage in glucuronide-saponins, has been shown to be applicable for the cleavage of the galacturonide linkage in 9.

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In the course of screening of natural products for platelet aggregation inhibitor in rabbit and human platelet, the extracts of Anemarrhenae Rhizoma was found to inhibit adenosine diphosphate (ADP)-induced platelet aggregation. The active components were isolated by column chromatography monitoring inhibitory activity of platelet aggregation and identified as tiomosaponin A-III and markogenin-3-O-β-D-glucopyranosyl-(1→2)-β-D-galactopyranoside by means of spectroscopic analysis. Timosaponin A-III and markogenin glycoside were found to inhibit ADP-induced aggregation as well as 5-HT or arachidonic acid-induced aggregation of human platelet.

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Saponin compositions in soybeans of 18 different origins were examined and it has been found that the content of acetyl-soyasaponins A₁ (8a), A₂ (9a), A₃ (10a), A₄ (11a), A₅ (12a), and A₆ (13a) [with soyasapogenol A (1) as the aglycone] varies depending upon the kind and the habitat. Saponins in seed coat, cotyledon, and hypocotyl of soybeans from U.S.A., China, and Hokkaido, were examined by thin layer chromatography and high performance liquid chromatography, and quantitatively analyzed by gas liquid chromatography. It has been found that seed coat does not contain saponin, whereas cotyledon contains saponin of soyasapogenol B (2) in 0.14-0.18% and saponin of soyasapogenol A (1) in 0.07-0.09%. It has been also found that the saponin content in hypocotyl is much higher than that in cotyledon, i.e. soyasapogenol B (2)-saponin in 0.42-0.52% and soyasapogenol A (1)-saponin in 1.25-1.46%. During these studies, a new saponin named soyasaponin V {7, 3-O-[β-D-glucopyranosyl-(1→2)-β-D-galactopyranosyl-(l→2)-β-D-glucuronopyranosyl]soyasapogenol B} was isolated from hypocotyl and the structure has been determined.

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Effects of iridoid glycosides on sex- and learning-behaviours induced by chronic"hanging stress"in mice, were studied. Drugs at a dose of 50 mg/kg were given orally every day after the exposure to stress. Geniposide and geniposidic acid showed a protective effect against decrease in sex behaviours, acceleration of extinction of memory, increase in failure of retrieval of memory, decrease of rectal temperature and enlargement of adrenal gland induced by the exposure to stress. Genipin showed a protective effect against decrease in licking, acceleration of extinction of memory, increase in failure of retrieval of memory and enlargement of adrenal gland, but promoted decrease in rectal temperature. Monotropein and gardenoside showed a weak protective effect against decrease in sex behaviours and acceleration of extinction of memory. Catalpol, aucubin and mussaenoside showed a weak protective effect against acceleration of extinction of memory, and mussaenoside showed an additional protective effect against increase in failure of retrieval of memory and decrease in rectal temperature.

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Reaction of 2-chloroquinoxaline (I) and C-nucleophiles (benzyl cyanide (IIa), acetonitrile (IIa), diethyl malonate (IIc), ethyl cyanoacetate (IId), malonodinitrile (IIe), nitromethane (IIf), phenylacetylene (IIg)) was carried out in hexamethylphosphoramide in the presence of potassium hydroxide. IIa, c-e afforded α-phenyl-2-quinoxalineacetonitrile (IIIa), diethyl 2-quinoxalinemalonate (IIIc), ethyl α-cyano-2-quinoxalineacetate (IIId) and 2-quinoxalinemalonodinitrile (IIIe) in fairly good yield, respectively.

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