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Cardiac glycosides and pregnanes from the roots and the stems of Adenium obesum Roem. et Schult. were investigated. Among 30 cardiac glycosides including 15 known glycosides and 15 new combinations of the known aglycones and sugars, the structures of 11 glycosides were elucidated. Oleandrigenin beta-gentiobiosyl-beta-D-thevetoside was the main glycoside. Neridienone A and 16,17-dihydroneridienone A, common pregnanes in Apocynaceae, were also isolated.

From the leaves of Alstonia scholaris , collected in Taiwan, Thailand, Indonesia and Philippines, several new alkaloids, 19-epischolaricine, N b -methylscholaricine, N a -methylburnamine and vallesamine N b -oxide were isolated and their structures determined by spectral and chemical methods. The leaves of plants from Taiwan and Thailand showed similar alkaloid patterns, with picrinine, nareline and alschomine as the major alkaloids. The leaves of plants from Indonesia and Philippines showed different patterns from those of plants from Taiwan or Thailand, and contained mainly angustilobine B group. Picraline and its homologues were obtained from the leaves of Indonesian plants.

In addition to ten alkaloids previously described, we have isolated two alkaloid N-oxides from Tylophora tanakae MAXIM. (Asclepiadaceae). Further, the polar fraction of the leaves and caules of this plant cultivated in a farm afforded two new polar alkaloids. The structures of the four products were determined. The relation between the structure and cytotoxic activity of this group of alkaloids is discussed.

Six new bisabolane-type sesquiterpenes, peroxylippidulcines A-C (3-5), peroxyepilippidulcine B (6), and epilippidulcines B (7) and C (8), have been isolated from the aerial parts of Lippia dulcis, along with two known bisabolane-type sesquiterpenes, seven known flavonoids, and a known triterpenoid. The structures of 3-8 were characterized on the basis of NMR, MS, specific rotation, and X-ray crystallographic analysis data and chemical evidence.

Further study of the methanol extract of the aerial parts of Physalis angulata (Solanaceae) resulted in the isolation of new withanolides, designated physagulins L, M and N, together with known withanolide, physagulin D and flavonol glycoside, quercetin 3-O-rhamnosyl-(1--6)-galactoside. The chemical structures of these new withanolides were elucidated by detailed spectroscopic analyses to be (20R,22R)-15alpha-acetoxy-5alpha,6beta,14beta,17beta,27-pentahydroxy-1-oxo-witha-2, 24-dienolide, (20S,22S)-15alpha-acetoxy-5alpha,6beta,14alpha,23beta-tetrahydroxy-1-oxo-witha-2,16,24-trienolide and (20S,22R)-15alpha-acetoxy-5beta,6beta-epoxy-14alpha-hydoxy-3beta-methoxy-1-oxo-witha-16,24-dienolide, respectively. All these compounds showed weak trypanocidal activity against trypomastigotes, an infectious form of Trypanosoma cruzi, the etiologic agent for Chagas' disease. Withanolides obtained in the previous paper showed considerable trypanocidal activity, suggesting the structure-activity relationships.

Crude extracts of Mexican medicinal plants were screened for trypanocidal activity against Trypanosoma cruzi, which is the etiological agent for Chagas' disease, one of the most serious protozoan diseases in Latin America. There were 71 kinds of methanolic and other organic extracts from 65 plants, which were newly examined by a preliminary screening test to observe immobilization of epimastigotes and trypomastigotes of T. cruzi in vitro. The MeOH extract of seeds of Persea americana (avocado) showed moderate activity against epimastigotes. In order to identify the principal compounds for the activity, the MeOH extract was subjected to bioassay-guided fractionation. From the active fractions, six 1,2,4-trihydroxyheptadecane derivatives and two 1,2,4-trihydroxynonadecane derivatives including a new one were isolated. These compounds showed moderate activity against epimastigotes and trypomastigotes.

Polyhydroxy-dinormonoterpenoids and their apiosylglucosides were obtained from the polar fraction of the leaves of Thevetia peruviana.

The hexane, acetone and methanol extracts of Calophyllum brasiliense leaves were fractionated following a three bioassay guide: high HIV-1 RT inhibition, low cytotoxicity on MT2 cells and high inhibition of HIV-1 IIIb/LAV replication. This led to the isolation of three anti HIV-1 dipyranocoumarins: calanolides A and B and soulattrolide. In contrast, other isolated compounds such as apetalic acid, isoapetalic acid, a structural isomer of isoapetalic acid, friedelin, canophyllol and amentoflavone were devoid of HIV-1 RT inhibitory activity. Calanolide C was also obtained as a natural product and showed moderate inhibitory properties.

The constituents of the aerial parts of Physalis angulata (Solanaceae) were investigated based on the plant's trypanocidal activity against epimastigotes of Trypanosoma cruzi, the etiologic agent for Chagas' disease. Four new withanolides were isolated, along with six known ones, from the active fraction. Their structures were determined by spectroscopic analysis. Trypanocidal activity against trypomastigotes, an infectious form of T. cruzi, was also estimated, as well as cytotoxic activity against human uterine carcinoma (HeLa) cells in vitro. Evaluation of trypanocidal activity using the colorimetric reagent Cell Counting Kit-8 was also examined.

The constituents of the stem bark of Garcinia subelliptica (Guttiferae) were investigated based on its trypanocidal activity against epimastigotes of Trypanosoma cruzi, the etiologic agent for Chagas' disease. As the active components, nine xanthones were isolated including two new ones, 4-hydroxybrasilixanthone B and 1,3,5,6-tetrahydroxy-4,7,8-tri(3-methyl-2-butenyl)xanthone. Their structures were determined by spectroscopic analysis. Trypanocidal activity against trypomastigotes, an infectious form of T. cruzi, was also estimated as well as cytotoxic activity. Fukugetin, the major component of the bark, showed no activity.

Thirty-two extracts from 22 Mexican medicinal plants of 15 different families were assayed to determine their antibacterial activity against Escherichia coli and Staphylococcus aureus. Seventeen plants showed antibacterial activity, while five plants showed no activity against both bacteria. All of the extracts showed higher activity against Staphylococcus aureus (methicillin-sensitive and methicillin-resistant) than against Escherichia coli, except one. Among the plants examined, Bursera simaruba (L.) Sarg. (Burseraceae), Haematoxylum brasiletto H. Karst. (Fabaceae), Calophyllum brasiliense Cambess. (Clusiaceae), and Mammea americana L. (Clusiaceae) were highly active against Staphylococcus aureus. Coumarins (mammea A/BA and mammea A/AA) and xanthones, namely jacareubin and 1,3,5,6-tetrahydroxy-2-(3,3-dimethylallyl) xanthone, were isolated as the principle compounds from the last two plants.

The MeOH extract of the leaves of rosemary (Rosmarinus officinalis L.) completely inhibited the motility of cultured epimastigotes of Trypanosoma cruzi at the concentration of 2 mg/ml after 2 h of incubation. Activity-guided fractionation of the MeOH extract has resulted in the isolation of three triterpene acids, betulinic, oleanolic and ursolic acids. Ursolic acid stopped the movement of all T. cruzi epimastigotes at the minimum concentration (MC(100)) of 40 micro g/ml (88 micro M) after 48 h of incubation. Oleanolic acid was less active (MC(100): 250 micro g/ml, 550 micro M) and betulinic acid was practically inactive.

From leaves and stems of Leuconotis eugenifolius , six indole alkaloids were isolated and five were identified as yohimbine, β-yohimbine, leuconolam, 21- O -methyl-leuconolam and rhazinaline N b -oxide. The new alkaloid, having a pentacyclic diazaspiro system, was determined to be a diazaspiroleuconolam and named leuconoxine. Other constituents identified were 3β-hydroxy-5α,6α-epoxy-β-ionone, epigallocatechin, loganic acid, 2-methyl-3-buten-2-ol rutinoside and four flavonol glycosides.

Thirteen compounds including four megastigmanes and five flavonoids were isolated and their structures were characterized. One of the megastigmanes, scorospiroside, was a new compound and elucidated as 3,5-dihydroxy-6,9-epoxymegastigmane-3- O -β- d -glucoside.

Affinosides Lf and Lg, both having the 11α-hydroxy-12-keto function in ring C, were isolated along with other known cardenolide glycosides from fresh leaves of Anodendron affine . The β- d -glucosides of Δ 16 -digitoxigenin and its 3α-epimer were also obtained.

The constituents of the leaves of Clerodendron bungei STEUD. (Verbenaceae) and leaves and bark of C. trichotomum THUNB. were investigated guided by the antiproliferative activity against three tumor cell lines (MK-1: human gastric adenocarcinoma, HeLa: human uterus carcinoma, and B16F10: murine melanoma). Two phenylethanoid glycoside caffeic acid esters, acteoside and isoacteoside, were isolated as the constituents which selectively inhibit the growth of B16F10 cells. The antiproliferative activities against B16F10 cells of acteoside (GI50: 8 microM), isoacteoside (8 microM) and their methanolysis products, methyl caffeate (26 microM), 3,4-dihydroxyphenethyl alcohol (8 microM), 3,4-dihydroxyphenethyl glucoside (10 microM), desrhamnosyl acteoside (6 microM), and desrhamnosyl isoacteoside (6 microm) suggested that the 3,4-dihydroxyphenethyl alcohol group might be more responsible for the activities of acteoside and isoacteoside than the caffeoyl group. The activities of chlorogenic acid, 3,4-dihydroxyphenylacetic acid, 3-(3,4-dihydroxyphenyl) alanine, 3,4-dihydroxy-phenethylamine hydrochloride, ferulic acid, sinapic acid, and five dihydroxybenzoic acids were also determined and compared with those of the above compounds.

Five new megastigmane glucosides and one of their aglycones were isolated, along with (6S,9R)-roseoside, from the polar fraction of the leaves of Asclepias fruticosa, and the structures were determined by spectroscopic methods. Most of them have an epoxy-linkage between C-5 and C-11. The configurations at C-3 and C-9 for each compound were confirmed to be S and R, respectively, by application of the modified Mosher's method.

3-Demethyl-14alpha-hydroxyisotylocrebrine N-oxide was isolated along with three homologous isotylocrebrine type alkaloids from the imagines and pupae of Ideopsis similis reared on the host plant, Tylophora tanakae.

Five new megastigmane glucosides and one of their aglycones were isolated, along with (6S,9R)-roseoside, from the polar fraction of the leaves of Asclepias fruticosa, and the structures were determined by spectroscopic methods. Most of them have an epoxy-linkage between C-5 and C-11. The configurations at C-3 and C-9 for each compound were confirmed to be S and R, respectively, by application of the modified Mosher's method.

Anodendrosins J and K, two diesters of 4-O-glycosyl-3, 5-diprenyl-4-hydroxybenzoic acid with sucrose were obtained from the seeds of Anodendron affine, and their structures were determined by spectral and chemical means.

Steroidal compounds in the roots of Asclepias tuberosa were investigated and 17alpha-hydroxyandrosta-4,6,15-trien-3-one 17-O-alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside, termed ascandroside, was isolated from the CHCl3-soluble fraction. Among five doubly-linked cardenolide glycosides, two were identified as 3'-spiro-linked thiazolidinone (4) and S-oxythiazolidinone derivatives (5) of delta5-calotropin. The stereochemistry at the C-3' in these two cardenolides is discussed. 3'-O-beta-D-Glucopyranosyl-delta5-calotropin (3) was also isolated along with A5-calotropin and its 3'-acetate. Nine glycosides of uzarigenin, coroglaucigenin and corotoxigenin were identified.

Thirteen pregnane glycosides were isolated from fresh leaves of Marsdenia tomentosa collected in the Fukuyama district. Of these, six were glycosides previously obtained from the same plant collected in the Fukuoka district and one from another Asclepiadaceous plant. The structures of the six new glycosides were determined by spectrometric method.

Parsonsianidine, a new minor macrocyclic pyrrolizidine alkaloid having two ethyl side-chains at C-11 and C-20, was isolated along with parsonsianine from the leaves of Parsonsia laevigata . Its structure was determined by spectral analyses. 17-Methylparsonsianidine, having the same plane structure as spiranine, was also identified.

3'-epi-19-Norafraside, a 19-norcardenolide glycoside with dual linkages between a cardenolide and 4, 6-dideoxy-galactos-2-ulose, and 12β-hydroxycoroglausigenin were newly isolated from the stems of Asclepias curassavica, along with known glycosides and free cardenolides. The structures were determined by spectral and chemical methods.

Three new tetrahydrofuranoid-lignan glycosides, tanegosides A, B and C, were isolated from Trachelospermum liukiuense HATSUSIMA, along with 8 lignan glycosides already known in T. asiaticum, and the structures were elucidated by spectral and chemical methods.

Parsonsianine, a 14-membered macrocyclic pyrrolizidine alkaloid, composed of retronecine, (2S, 3R)-2, 3-dihydroxy-2-ethylbutanoic acid and (2R, 3S)-2, 3-dihydroxy-2-isopropylbutanedioic acid, was isolated from the leaves of Parsonsia laevigata and the structure was determined by means of nuclear magnetic resonance and X-ray analysis.

2'-O-Acetyl-β-D-thevetosides and β-D-glucosyl(1→4)-2'-O-acetyl-β-D-thevetosides of oleandrigenin and digitoxigenin were isolated along with D-cymarosides, D-thevetosides and D-digitalosides from the roots and the stems of Adenium obesum ROEM. et SCHULT. 4-O-β-D-Glucopyranosyl-D-cymaritol was isolated from the polar fraction.

From the bark of Meliosma lanceolate, nine triterpenoid glycosides including the 28-O-β- d -glucopyranosyl ester of bayogenin -3-O-β- d -glucuronopyranoside , its 4′-O-β- d -galactopyranoside and 4′-O-α- l -arabinopyranoside were isolated and the structures characterized along with that of 28-O-β- d -glucopyranosyl-bayogenin -3-O-β- d -4′- anhydro -4′,5′- didehydroglucuronopyranoside . Bisdesmosidic triosides of hederagenin were obtained as minor components.

From the leaves of Thevetia peruviana four new flavonol glycosides, kaempferol 3-glucosyl(1 --> 4) [6"'-sinapoylglucosyl] (1 --> 2) galactoside and 3-[2""-sinapoylglucosyl](1 --> 4)[6"'-sinapoylglucosyl](1 --> 2)galactoside and kaempferol and quercetin 3-[6"'-sinapoylglucosyl](1 --> 2)galactoside were isolated, together with the known compounds, kaempferol and quercetin 3-glucosyl(1 --> 2)galactoside. The glycosides were characterized from FAB mass, 1H and 13C NMR and UV spectral data.

We have previously reported that the SPF-conditioned LEC/Otk rat has characteristic pathological features. (1) Jaundice develops in almost all rats with increase in the plasma glutamic pyruvic transaminase (P-GPT) level. (2) The animals show episodes of jaundice, a high P-GPT level, and liver cell necrosis, but only slight inflammatory cell infiltration. (3) The liver cells show characteristic microvesicular fatty changes. (4) The P-GPT level shows increases, first at 18 weeks and then at 25 weeks of age. (5) The rats show immunological disorders, such as deficiency of immunoglobulins, especially IgG1, and of helper T cells [1].

A mutant strain of rats, LEC, that develops spontaneous hepatic injury associated with severe jaundice was developed in 1987 [1]. In this LEC strain, isolated and established as an inbred strain by sibmating, almost 90% of the animals show hereditary hepatic injury in conventional conditions [2, 3]. Genetic analysis indicated that at least one autosomal recessive gene is responsible for this disease [4]. Thus, the LEC strain is a useful model for studies on liver cell injury and liver cancer. Hepatocellular carcinomas have been found in LEC rats surviving for a long time after recovery from jaundice [2, 5]. Hepatocellular carcinomas were also found in all cases in the present study, as will be reported in detail (Chap. III. p. 2).

Cardiac glycosides from Beaumontia brevituba and B. murtonii were examined. Gentiobiosyl-β- d -cymaroside and gentiobiosyl-α- l -cymaroside of digitoxigenin were isolated from the seeds, unripe fruits, and leaves of B. brevituba , and the leaves of B. murtonii . Oleandrigenin and/or Δ 16 -digitoxigenin glycosides having the same sugar moieties were not isolated from the leaves of B. brevituba but from the leaves of B. murtonii as well as the seeds of B. brevituba .

Two minor iridoids isolated from the leaves of Thevetia peruviana were shown to be 10-O-β- D -fructofuranosyltheviridoside and 6′-O-β- D -glucopyranosyltheviridoside .

10-O-β-D-Glucopyranosyltheviridoside and 3'-O-β-D-glucopyranosyltheviridoside were obtained from the roots of Thevetia peruviana along with the major iridoids, theviridoside and theveside, and minor ones, recently obtained from the leaves, 10-O-fructofuranosyltheviridoside and 6'-O-glucopyranosyltheviridoside.

A new pyrrolizidine alkaloid, 14-deoxyparsonsianidine N-oxide, was isolated from adults of a danaine butterfly, Idea leuconoe. The compound appears to have been incorporated directly from the host plant, Parsonsia laevigata, together with other major analogs, during the larval stage.

From leaves of Nerium indicum, along with cardenolide glycosides, two minor pregnane glucosides were isolated and the structures elucidated as 3-O-β-gentiobiosyl-3β,14-dihydroxy-5α,14β-pregnan-20-one and 21-O-β- d -glucosyl-14,21-dihydroxy-14β-pregn-4-ene-3,20-dione.

10-O-Benzoyltheveside and 10-dehydrogeniposide were isolated from the fresh leaves of Cerbera manghas along with loganin, theviridoside and theveside. The structures were established by spectral and chemical methods.

(+)-Abscisyl β-D-glucopyranoside was isolated from mature Citrus unshu peelings as a germination inhibitor component. This is the first report of the direct isolation of (+)-abscisyl β-D-glucopyranoside from this source.

Bis- O -rhamnosides of lariciresinol, 5,5′-dimethoxylariciresinol and secoisolariciresinol, and pinoresinolapiosyl (1 → 2)-glucoside were isolated from Parsonsia laevigata .

Eight glycosides of 2α, 19α-dihydroxyoleanolic acid derivatives, includingtrachelosperosidesD-1, D-2, E-1, F-2, and arjungenin-23, 28-bis-Ο-glucoside and-28-Ο-xylopyranosyl- (1→2) -gluco-pyranoside, were isolated from the whole plant of Trachelospermum asiaticum, along with the known glucosides arjunglucoside I and arjungenin-3, 28-bis-Ο-glucoside, and their structures were determined.

Cardenolide glycosides, affinosides A, C, D, E, F, G, H and J, were isolated from the stem and bark of Anodendron affine DRUCE, and their structures were elucidated. They have the same sugar moiety as affinoside B, 4, 6-dideoxy-3-O-methyl-D-glycero-D-glycero-2-hexosulopyranose, which is doubly linked to the 2α- and 3β-hydroxyl groups of the aglycone with 2'-acetal and 1'-anomeric hydroxyl groups, respectively. The aglycone of A was identified as 2α, 3β, 11α, 14-tetrahydroxy-12-oxo-14β-carda-4, 20 (22)-dienolide-7β, 8β-epoxide. The others were found to be 2α, 3β, 14-trihydroxy-11-oxo-, 2α, 3β, 12α, 14-tetrahydroxy-11-oxo-, and 2α, 3β, 5, 12α, 14-pentahydroxy-11-oxo-5β, 14β-card-20 (22)-enolide (C, E, and G, respectively), and 2α, 3β, 12β, 14-tetrahydroxy-11-oxo-14β-carda-4, 20 (22)-dienolide (F). H, D, and J were Δ16-derivatives of A, C, and F, respectively. C was hydrolyzed to the aglycone by preliminary splitting of the 2-O-2'linkage by NaBH4 reduction, followed by treatment with HCl / acetone.

Esters of p-O-glucosyl-and p-O-primverosylnervogenic acid with some carbohydrates (including dambonitol, glucose, and sucrose) were isolated from the seeds, unripened fruits, and caules of Anodendron affine DRUCE. The locations of the nervogenic acid moiety on dambonitol and sucrose were determined on the basis of spectral and chemical evidence.