A. San Feliciano

Antitumor properties of podophyllotoxin and related compounds.

The lignan family of natural products includes compounds with important antineoplastic and antiviral properties such as podophyllotoxin and two of their semisynthetic derivatives, etoposide and teniposide. The latter are included in a wide variety of cancer chemotherapy protocols. Due to these biological activities, lignans, and especially cyclolignans, have been the objective of numerous studies focused to prepare better and safer anticancer drugs. The mechanism by which podophyllotoxin blocks cell division is related to its inhibition of microtubule assembly in the mitotic apparatus. However, etoposide and teniposide were shown not to be inhibitors of microtubule assembly which suggested that their antitumor properties were due to another mechanism of action, via their interaction with DNA and inhibition of DNA topoisomerase II. Other podophyllotoxin derivatives has also been reported which retained or even improved the cytotoxic activity, but these were weak inhibitors of topoisomerase II in vitro; the data revealed that such analogs exhibit a different, as yet unknown, mechanism of action. The main deficiency of these compounds is their cytotoxicity for normal cells and hence side effects derived from their lack of selectivity against tumoral cells. In this regard it is necessary to investigate and prepare new more potent and less toxic analogs, that is, with better therapeutic indices. It is well accepted from structure-activity studies in this field that the trans-lactones are more potent as antineoplastics than the cis-lactones. Not only the configuration of the D ring is an important factor for high cytotoxic activity, but also a quasi-axial arrangement of the E ring is necessary. On this basis, studies on lignans have been addressed to modify the lactone moiety and prepare analogs with heteroatoms at different positions of the cyclolignan skeleton. Our group has been working during the last few years on chemical transformations of podophyllotoxin and analogs and we have prepared a large number of cyclolignan derivatives some of which display potent antiviral, immunosuppressive and cytotoxic activities. We have reported several new cytotoxic agents with nitrogen atoms at C-7 or C-9 or at both C-7 and C-9: imine derivatives, oxime derivatives, pyrazoline-, pyrazo- and isoxazoline-fused cyclolignans. At present, we are preparing mainly new compounds by modifications of the A and E cyclolignan-rings. They are being tested on cultures of different tumoral cell lines (P-388 murine leukemia, A-549 human lung carcinoma, HT-29 human colon carcinoma and MEL-28 human melanoma) and some of them have shown an interesting and selective cytotoxicity.

Terpenoids from leaves of Juniperus thurifera

Abstract Nineteen diterpenoids of the labdane, pimarane and abietane skeletons and four known sesquiterpenoids were isolated from Juniperus thurifera leaves. Thirteen of these diterpenoids are described for the first time as natural products. Their structures were elucidated principally by NMR techniques and chemical transformations.

Asteriscanolide: a sesquiterpene lactone with a new natural skeleton

Abstract A sesquiterpene lactone was isolated from the hexane extract of Asteriscus aquaticus . Its constitution and stereochemistry were determined by spectroscopic techniques, principally two-dimensional NMR correlations (COSY, HCCORR, RELAY) and with the interpretation of certain chemical transformations. The results were confirmed by X-ray diffraction and the name asteriscane is proposed for the new natural skeleton.

New natural diterpene acids from Juniperus communis

Abstract Three new diterpene acids have been isolated from the leaves of Juniperus communis and their structures, elucidated by spectroscopic methods, were identified as 7-oxo-13-epi- pimara-8,15-dien-18-oic acid, 7α-hydroxysandaracopimaric acid and (14 S)-14,15-dihydroxylabda- 8(17),13(16)-dien-19-oic acid. Biflavonyls, fatty acids and diterpenoids with known structures were also isolated.

Aquatolide. A new type of humulane-related sesquiterpene lactone

Abstract A new sesquiterpene lactone called aquatolide was isolated from the hexane extract of Asteriscus aquaticus . Its constitution and stereochemistry were deduced from spectroscopic data, mainly homonuclear and heteronuclear two-dimensional NMR correlations.

Antipyretic, Hypothermic and Antiinflammatory Activities and Metabolites from Solanum ligustrinum Lood.

The acute toxicities of the global methanol extract of Solanum ligustrinum (Solanaceae) and the crude steroidal glycoalkaloids mixture were determined. The antipyretic, hypothermic and antiinflammatory activities of aqueous, global methanol, petroleum ether, dichloromethane and methanol extracts and crude steroidal glycoalkaloids mixture of the aerial parts were evaluated.

Asteriscunolides A, B, C and D, the first humulanolides; Two pairs of conformationally stable stereoisomers

Abstract Following a preliminary comunication on Asteriscunolide A (the first reported natural humulanolide), three more configurationally and/or conformationally isomeric Asteriscunolides ( B, C and D ) from the same plant ( Asteriscus aquaticus L.) are described. The absolute configurations and the stable conformations of all four Asteriscunolides are established by an array of spectroscopic methods (CD, 1H and 13C NMR) without resorting to X ray analysis.

Eudesmane glycosides from Carthamus lanatus

Abstract Two new eudesmane glycosides, intermedeol β- d -fucopyranoside and its 2′ α-methylbutyrate, were isolated from the hexane extract of Carthamus lanatus and their structures established by spectral and chemical means.

Saccharinic acid lactone from Astragalus Lusitanicus lam. (−)-2-c-methyl-d-erythrono-1,4-lactone☆☆☆

Abstract (−)-2-C-methyl-D-erythrono-1,4-lactone has been isolated from A. lusitanicus , its structure being established by spectroscopic methods and synthesis. This is the first report of a natural saccharinic acid lactone.

Asteriscunolide A: Humulanolide from asteriscus aquaticus

A number of humulanolides and other sesquiterpene lactones have been isolated from Asteriscus aquaticus (L). The structure, absolute stereochemistry and conformation of the major component, asteriscunolide A, have been determined.