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From a cytotoxic Et2O-soluble extract of Muntingia calabura roots, twelve new flavonoids were isolated, constituting seven flavans 1-7, three flavones 8, 10, and 12, and two biflavans 9 and 11. The structures of compounds 1-12 were established by the interpretation of spectral data, with the nmr assignments of these constituents being based on 1H-1H COSY, 1H-13C HETCOR, and selective INEPT experiments. This is the first report of the occurrence of 7,8-di-O-substituted flavans, biflavans, and flavones. Most of the isolates demonstrated cytotoxic activity when tested against cultured P-388 cells, with the flavans being more active than the flavones. Furthermore, certain of these structurally related flavonoids exhibited somewhat selective activities when evaluated with a number of human cancer cell lines.

Following bioassay-directed fractionation procedures, two 7-oxygenated-8-prenylflavones, (-)-pseudosemiglabrin [1] and (-)-semiglabrin [2], were isolated from an MeOH extract of Tephrosia semiglabra. (-)-Pseudosemiglabrin [1] displayed in vitro inhibitory effects on human platelet aggregation.

In addition to known triterpenoids maniladiol [6] and serrat-14-ene-3 beta,21 alpha-diol [7], two new compounds, one oleanane derivative designated as 28-acetoxyerythrodiol [1] and one isoflavone designated as 5,4'-dimethoxy-3'-prenylbiochanin A [5], have been isolated and characterized from the CHCl3 extract of the stem bark of Erythrina eriotriocha. Their structures have been established on the basis of the spectrocopic techniques (ir, nmr, uv, ms) and chemical evidence.

Two new compounds, a long chain ester 1 of p-coumaric acid and a prenylated isoflavone, senegalensin [5], 5,4'-dihydroxy-8-(gamma,gamma-dimethylallyl)-[5"-(hydroxyisopropyl ) (2",3":6.7)] isoflavone, in addition to a known long chain ester 2 of ferulic acid, have been isolated and characterized from the stem bark of the Cameroonian medicinal plant Erythrina senegalensis. Another known compound 3, a long chain ester of ferulic acid, was isolated from Erythrina excelsa. The structures of all the compounds were determined by spectroscopic techniques.

The flowers of Quararibea funebris have yielded another new pyrrole lactone alkaloid, named funebradiol [1]. This compound was elucidated by the use of nmr, ir, and mass spectral interpretation. A potentially new biosynthetic pathway is postulated.

By bioactivity-directed fractionation, six cytotoxic constituents have been characterized from the bark of Plumeria rubra collected in Indonesia. Three iridoids, fulvoplumierin [1], allamcin [2], and allamandin [3], as well as 2,5-dimethoxy-p-benzoquinone [4], were found to be active constituents of the P. rubra petroleum-ether- and CHCl3-soluble extracts. Cytotoxic compounds isolated from the H2O-soluble extract of the bark were the iridoid plumericin [5], and the lignan liriodendrin [6]. Each of these substances was found to demonstrate general cytotoxic activity when evaluated with a panel of cell lines composed of murine lymphocytic leukemia (P-388) and a number of human cancer cell-types (breast, colon, fibrosarcoma, lung, melanoma, KB). Five additional iridoids, 15-demethylplumieride [7], plumieride [8], alpha-allamcidin [9], beta-allamcidin [10], and 13-O-trans-p-coumaroylplumieride [11], were obtained as inactive constituents. Compound 7 was found to be a novel natural product, and its structure was determined by spectroscopic methods and by conversion to plumieride [8]. The configuration of the C-4 stereocenter was unambiguously assigned for compounds 9 and 10, and certain nmr reassignments have been provided for compound 1.

Two new macrocylic alkaloids, 11-epi-ephedradine A (11-epi-orantine) [1] and schweinine [2], were isolated from the whole plant of Schweinfurthia papilionacea, in addition to (-)-ephedradine A (orantine) [3]. Their structures were determined by spectroscopic means, and the stereochemistry has been assigned on the basis of 2D nmr techniques.

Four cis-ent-neoclerodane lactones, amphiacrolide A [2], amphiacrolide B [3], amphiacrolide C [4] and amphiacrolide D [5] were isolated from the aerial parts of Amphiachyris dracunculoides, and their structures established by physical and chemical methods. High field 1H- and 13C-nmr assignments were made for each compound and some of their derivatives by using one- and two-dimensional nmr techniques including nOe difference, COSY, and CH-correlation of one-bond and multiple bond (COLOC) relationships. A chemical correlation of the amphiacrolides to gutierolide [1], a compound with absolute stereochemistry determined by X-ray analysis, established the stereochemistry for the group. Consequently, a compound having reported properties identical with amphiacrolide D [5] must have its structure revised to contain the beta-faced epoxide. Amphiacrolide A [2] had not been reported previously.

Three sesquiterpene evoninoate alkaloids, hippocrateine I [1], hippocrateine II [2], and emarginatine A have been isolated from the root and stem barks of Hippocratea excelsa. Compounds 1 and 2 are new naturally occurring substances. The structure of 1 was unequivocally established by X-ray crystallographic analysis, and the structure of the second new alkaloid was deduced by spectral analysis.

An extract of the whole plant of Ruellia brittoniana has afforded the new glycoside 2-O-alpha-D-galactopyranosyl glycerol hexaacetate [1]. Its structure and absolute configuration were deduced by spectroscopic methods and X-ray crystallographic analysis.

Previous research on the aerial parts of Calendula arvensis led to the isolation of the epicubebol glycoside 1 and of the sesquiterpene glycosides 2-5 based on the alloaromadendrane skeleton. A further investigation has revealed two new glycosides, 6 and 7, derived from the same sesquiterpene, the structures of which were elucidated by spectral studies. Furthermore a series of antiviral tests has been performed on glycosides 1-7 by examining their ability to interfere with rhinovirus 1B and vesicular stomatitis virus infection in vitro. Only glycoside 1 slightly reduced rhinovirus multiplication. All the compounds were able to inhibit vesicular stomatitis virus infection, 1 and 2 being the most effective.

The aerial part of Artemisia douglasiana, used in folk medicine as a cytoprotective agent against the development of peptic ulcer, was studied, its active principle dehydroleucodine [1] isolated, and its pharmacological properties analyzed. In order to establish whether or not the reported activity is particular to sesquiterpene lactones, the study of the cytoprotective activity of several related guaianolides and pseudoguaianolides from plants was undertaken. Ludartin [3], 8-angeloyloxy-3-hydroxyguaia-3(15),10(14),11(13)-trien-6,12- olide [4], hymenin [5], mexicanin I [6], helenanin [7], and 9-O-desacetylsparthulin-2-O-angelate [8] were found to exhibit protection. Desacetoxymatricarin [2] did not show cytoprotective activity. The results obtained from the different sesquiterpene lactones studied suggest that the presence of the alpha-methylene-gamma-lactone moiety is, in principle, a requirement for the observed antiulcerogenic activity.

Three novel polyhydroxylated triterpenes have been isolated from Uncaria tomentosa. Their structures were established as 1, 2, and 3 by detailed spectral studies including 1H-13C correlations via long range couplings using the INAPT pulse sequence, nOeds, and 2D 1H-13C direct chemical shift correlation (HETCOR) nmr techniques.

A new triterpenoid saponin, 3-O-[alpha-L-rhamnopyranosyl (1----3)-beta-D-glucuronopyranosyl]-28-O-[beta-D-xylopyranosyl (1----2)-beta-D-glucopyranosyl]-3 beta-hydroxyolean-12-en-28-oate [3] has been isolated together with two known saponins, 3-O-[alpha-L-rhamnopyranosyl (1----3)-beta-D-glucuronopyranosyl]-3 beta- hydroxyolean-12-en-28-oic acid [1] and 3-O-[alpha-L-rhamnopyranosyl (1----3)-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-3 beta- hydroxyolean-12-en-oate [2], from the fruits of Deeringia amaranthoides.

The CH2Cl2 extract of Ferula sinaica afforded twelve sesquiterpenes including three new daucanes, 14-hydroxyvaginatin, 4 beta, 8 beta, 9 alpha-trihydroxy-6 alpha-p-hydroxy-benzoyloxydaucane, and isolancerotriol.

The southwestern Indian paintbrush, Castilleja linariaefolia, yielded extracts that displayed in vivo activity against murine P-388 (PS) lymphocytic leukemia. Separation guided by PS cell line inhibition led to isolation of cytotoxic compounds that were identified as the known glycosides acteoside [1] (ED50 2.6 micrograms/ml) and isoacteoside [2] (ED50 10 micrograms/ml). The identifications were established by spectral measurements and degradation studies. Mannitol was also found in this plant.

From the stem bark of Erythrina eriotriocha, a novel isoflavone, eriotriochin has been isolated and characterized, in addition to known compounds auriculatin, dihydroauriculatin, and 3'-O-methylorobol. The structure of compound 1 was determined by COSY, selective INEPT, 2D HMBC, NOESY, DEPT, and other spectroscopic techniques.

Two new nortriterpenoid saponins, designated yemuoside YM8 [1] and yemuoside YM9 [2], were isolated from Stauntonia chinensis. A new saponin 3 was obtained from the cleavage of the ester-glycoside linkage of 1 or 2. Structures were elucidated on the basis of chemical and physicochemical evidence.

Four new minor dihydro-beta-agarofuran-skeleton sesquiterpenes, 9 beta-benzoyloxy-1 alpha,2 alpha,6 beta-triacetoxy-15-hydroxydihydro-beta- agarofuran [1], 9 beta-benzoyloxy-1 alpha,2 alpha,6 beta,15-tetracetoxydihydro-beta-agarofuran [6], 9 alpha-benzoyloxy-1 alpha,2 alpha,6 beta-triacetoxy- 8 alpha,15-dihydroxydihydro-beta-agarofuran [7], and 9 alpha-benzoyloxy-1 alpha,2 alpha,6 beta,8 alpha-tetracetoxy-15- hydroxydihydro-beta-agarofuran [8] were isolated from the aerial parts of Maytenus chubutensis and identified by spectroscopy and chemical reactions.

Two new 14 alpha-methylsterols, roxburghiadiol A and roxburghiadiol B, were isolated from the leaves and fruits of Aglaia roxburghiana. Previously their structures were tentatively assigned as 4-bisnormethyl-24-methylene-cycloarta-3 beta, 7 alpha-diol and 4-bisnormethyl-24-methylene-cycloarta-3 beta, 6 alpha-diol, respectively. A reinvestigation using 2D-nmr technique has confirmed the structure 2 for roxburghiadiol B as previously reported, and roxburghiadiol A is now found to be the corresponding 6 beta epimer 1.

A novel phytoestrogen compound, 3'-prenyl-4'-methoxy-isoflavone-7-O- beta-D-(2''-O-p-coumaroyl)glucopyranoside, has been isolated from the EtOAc-soluble fraction of the stems of Sopubia delphinifolia and has been identified by chemical and spectral analysis. Pharmacological examination of the compound showed it to have estrogenic activity.

The cardiac effects of the leaf extract and 11 isolated pure compounds have been examined on isolated, spontaneously beating, atrial muscles of the rat. Using nor-adrenaline (8 X 10(-7)M) and acetylcholine (4 X 10(-8)M) as reference drugs and normal saline (equivalent volume) as control, the crude extract of Dysoxylum lenticellare (8 X 10(-4) g/ml) induced negative chronotropic and positive inotropic responses on the isolated cardiac muscle preparations. The extract demonstrated significant (p less than 0.05-0.01) cardioactivity as attested to by its positive inotropic and/or negative chronotropic activities on the rat atrial preparations. Of the pure isolates tested, 7, 8, and 9 demonstrated significant cardiac effects. Although the precise mechanism of action of the extract or pure isolates on the atrial myocardium has not been fully determined, available experimental data suggest that the extract and pure isolates act directly on the cardiac muscle. Alkaloids 7, 8, and 9 manifest cardiac effects similar to that of the crude extract but of lesser magnitude. Some indirect effects of these isolates may, however, be associated with the manifested activities.

The stem bark of the Thai tree Aquilaria malaccensis (Thymelaeaceae) has afforded 1,3-dibehenyl-2-ferulyl glyceride (3), which is novel, and 12-O-n-deca- 2, 4, 6-trienoylphorbol-13-acetate (4). The structures of these cytotoxic compounds were elucidated by their spectral and chemical parameters.

The leaves and roots of Rhazya stricta (Apocynaceae) yielded four indole alkaloids. Three of these isolated, vallesiachotamine (1), sewarine (3) and tetrahydrosecamine (4), displayed cytotoxic activity; polyneuridine (2) was not reported previously from this species. Tetrahydrosecaminediol (5), its acetate 6, and didemethoxycarbonyl-tetrahydrosecamine (7) were prepared from tetrahydrosecamine (4) by chemical reactions. The diol 5 was highly cytotoxic.

Arjunolic acid, an oleanene-type triterpene isolated from the rhizome of Cochlospermum tinctorium, its triacetate derivative, and their methyl esters were tested using the short-term in vitro assay on EBV-EA activation in Raji cells induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Their inhibitory effects on skin tumor promotors were found to be greater than those of previously studied natural products.

Extracts of Micromelum integerrimum (Buch.-Ham. ex Coleb.) M. Roem. were fractionated based on in vivo activity in mice in the P-388 lymphocytic leukemia system. Activity in ethanol extracts was concentrated in the chloroform partition fraction, which was further resolved by chromatography on silica gel. The known coumarins, micromelin and scopoletin, were crystallized from the active fractions and demonstrated to have antitumor activities. Micromelin was converted to the corresponding butenolide (deoxymicromelin) which was inactive in the 9KB assay.

Maquiroside A, a new cardiac glycoside, was isolated from the Peruvian plant Maquira calophylla. The structure was established using spectroscopic methods, and the aglycone was found to be cannogenol. The sugar portion was identified as D-cymarose. Maquiroside A demonstrated activity against the KB cell culture.

The cytotoxic drimane derivatives cinnamodial (1), capsicodendrin (2), a partially characterized tetramer of 1, and cinnamosmolide (3) were obtained from Capsicodendron dinisii (Canellaceae). A new compound, 6 beta-acetoxyisodrimenin (4) and ugandensolide (5) and futronolide (6) were also isolated, but were not cytotoxic.

Under the conditions delineated in this paper, alkaloid synthesis was not detectable in heterotrophic callus and suspension cultures of Heimia salicifolia. However, in vitro-grown shoots are active in alkaloid biosynthesis, yielding the biphenylquinolizidine lactones vertine (1), lytrine (5), and lyfoline (7), the ester alkaloids demethoxyabresoline (14) and epidemethoxylabresoline (11), the phenylquinolizidinols demethyllasubine-I (10) and demethyllasubine-II (12), and several minor alkaloids that had not been previously shown to occur in H. salicifolia.

In continuation with our work on the flavonoids of Sideritis species, we have now isolated and identified from Sideritis leucantha extracts, the novel flavonoid compound, isoscutellarein-7-O-[allosyl (1----2) glucoside].

Six components have been isolated from the bark of Michelia rajaniana, and their structures have been determined by spectroscopic analysis. Four of the components have been reported previously: The germacranolide (-)-parthenolide and the oxoaporphinoid alkaloid liriodenine have been observed as constituents of several species, and (-)-bisparthenolidine and (+)-paramicholide have been reported recently by us as constituents of Paramichelia baillonii. The two new components 3 and 4, which are novel derivatives of parthenolide and contain an unusual N-acetyl substituent at C-13, have been given the names (+)-N-acetylparthenolidine and (+)-N-acetyl-8 alpha-hydroxyparthenolidine, respectively. The crude CHCl3 extract of the bark of M. rajaniana exhibited strong cytotoxicity in the KB cell culture assay.

The bulbs of Pancratium littorale collected in Hawaii were found to contain a new phenanthridone biosynthetic product designated pancratistatin (4a) that proved to be effective (38-106% life extension at 0.75-12.5 mg/kg dose levels) against the murine P-388 lymphocytic leukemia. Pancratistatin also markedly inhibited (ED50, 0.01 microgram/ml) growth of the P-388 in vitro cell line and in vivo murine M-5076 ovary sarcoma (53-84% life extension at 0.38-3.0 mg/kg). An X-ray crystal structure determination of pancratistatin monomethyl ether (4c) and a detailed high resolution (400 MHz) nmr study of pancratistatin and its pentaacetate (4b) completed assignment of structure 4a. Companion antineoplastic constituents of P. littorale were found to be narciclasine (2c) and its 7-deoxy derivative (2a). The structure of 7-deoxynarciclasine (2c) was also confirmed by an X-ray crystallographic analysis.

From the leaves of Daphnopsis sellowiana (Thymelaeceae), 2'-hydroxyflavone [1], a rare natural product, has been isolated and characterized through its spectroscopic properties. Confirmation of the structure was achieved through total synthesis, which also afforded adequate material for complete 13C-nmr analysis.

16-Epi-Z-isositsirikine (1) has been isolated from the leaves of Catharanthus roseus and Rhazya stricta and identified through a combination of spectral interpretation and chemical correlation. The compound displayed antineoplastic activity in the KB test system in vitro and the P-388 test system in vivo.

Six tetrahydroprotoberberines, (+)-sinactine, apocavidine, stylopine, (+)-cavidine, cheilanthifoline, and dehydrocavidine; two spirobenzylisoquinolines, yenhusomine and yenhusomidine; one phthalideisoquinoline, corlumine; one benzophenanthridine, dihydrosanguinarine and protopine, have been isolated from the leaves and stems of Corydalis meifolia Wall. Of these alkaloids, dehydrocavidine was a new base. The remaining alkaloids, although known, were isolated for the first time for this plant. (+)-Cavidine, protopine, corlumine, yenhusomine, and dehydrocavidine exhibited spasmolytic activity.

Three new chromones, namely 10-(2',3'-dihydroxy-3'-methylbutanyl)-spatheliachromen, 10-(1',2',3'-trihydroxy-3'-methylbutanyl)spatheliachromen, and 6-(3'-hydroxy-3'-methyl-trans-but-1'-enyl)-O-methylisospatheliachrome n were isolated from the 10% aqueous MeOH extract of the twigs and leaves of Spathelia sorbifolia, together with five known chromones. Compound 2, the known spatheliabischromen, and 5-O-methylsorbifolin showed cytotoxicity against 9PS cells in culture.

An investigation of Witheringia coccoloboides (Dammer) A. T. Hunziker [Capsicum fuscoviolaceum (Cufodontis) Mort. And Standl.] roots has resulted in the isolation of two cytotoxic compounds: physalin B (1) and a novel physalin, which was characterized by spectral analysis as 25,26-epidihydrophysalin C (2). Both compounds have demonstrated cytotoxic activity in 9KB and 9PS tumor cells (in vitro). Physalin B (1) has demonstrated moderate activity against the 3PS mouse leukemia (in vivo).

Investigation of the MeOH extract of Exostema caribaeum (Rubiaceae) led to the isolation of three new 4-phenylcoumarins. Their structures, 5-O-beta-D-galactosyl-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin [1a] 7,4',5'-trihydroxy-4-phenyl-5,2'-oxidocoumarin [2a] and 7,4'-dimethoxy-5'-hydroxy-4-phenyl-5,2'-oxido-coumarin [3a] were elucidated by spectral methods and chemical transformations. It was also demonstrated that 4-phenylcoumarins undergo oxidative cyclization under basic conditions in the presence of air to give 4-phenyl-5,2'-oxido-coumarins.