[Diterpenes and other components of Croton hirtus (Euphorbiaceae)]. / Diterpenos y otros constituyentes de Croton hirtus (Euphorbiaceae).

The roots of Croton hirtus (Euphorbiaceae) collected in Paraiso, Cartago (Costa Rica) afforded, in addition to the few known metabolites, 20 new compounds: the bis-nor dolabradane 1, the dolabradanes 2 and 3, the kauranes 4-7, the cyclopropakauranes 8 and 9, the hirtusanes 10-15, the germacradiene esters 16-18 and the C-25 compound 21, presumably formed by a Diels-Alder reaction between compound 18 and a monoterpene. All structures were elucidated using high field 1D and 2D NMR techniques. MS fragmentation patterns are here reported. The absolute configurations of 4 and 9 were elucidated by using circular dichroism. The separation was performed with modern chromatographic technics.

Pure compound libraries; a new perspective for natural product based drug discovery.

What often distinguishes the leaders in drug discovery and development from the rest is the quality of their compound libraries and the ease of access that they have to the information within those libraries. The screening of natural products can provide greater structural diversity than standard synthetic chemistry and offers significant opportunities for finding novel low molecular weight lead compounds. However, which strategy is the best for natural-product-based drug discovery? Two well established but relatively time consuming approaches are the screening of crude extracts and pre-fractionated extracts. This case study describes a third, pure-compound-screening approach, and discusses its benefits and pitfalls.

In vitro antiplasmodial activity of 4-phenylcoumarins from Exostema mexicanum.

The stem bark of Exostema mexicanum (Rubiaceae) is used in Latin American folk medicine as a quinine substitute for malaria treatment. Bioassay-guided fractionation of lipophilic and hydrophilic extracts from the stem bark and branches yielded two previously undescribed 4-phenylcoumarins: 4',8-dihydroxy-5,7-dimethoxy-4-phenylcoumarin (exomexin A) and 3',4'-dihydroxy-5,7,8-trimethoxy-4-phenylcoumarin (exomexin B). Together with five known derivatives the in vitro activities against a chloroquine-sensitive strain (poW) and a chloroquine-resistant strain (Dd2) of Plasmodium falciparum have been evaluated. The most lipophilic compound, 4',5,7,8-tetramethoxy-4-phenylcoumarin (O-methylexostemin) revealed the strongest antiplasmodial activity (IC50 values: 3.6 microg/ml [poW], 1.6 microg/ml [Dd2]).

Diterpenes and other constituents from Croton draco (Euphorbiaceae)

Croton draco (Euphorbiaceae) from Guadalupe, San José, Costa Rica was collected in July 1992 and phytochemically studied (leaves, seeds, wood, bark, sap and flowers separately). Commonly known compounds such as 1-hydroxyjunenol, p-hydroxybenzaldehyde, p-methoxybenzoic acid, 3,4,5-trimethoxycinnamyl alcohol, the coumarin scopoletin, the nor-terpenoids 9-dehydrovomifoliol and 2,3-dihydrovomifoliol were obtained. Taspine, two aporphinic alkaloids, the diterpenes 9(11)-dehydrokaurenic acid, hardwikiic acid, the corresponding new 12-oxo derivative as well as five clerodanes and a phorbol ester were also isolated. Three clerodanes were not previously described and their NMR spectroscopical data and MS fragmentation patterns are reported.

Diterpenes and other constituents from Croton draco (Euphorbiaceae).

Croton draco (Euphorbiaceae) from Guadalupe, San José, Costa Rica was collected in July 1992 and phytochemically studied (leaves, seeds, wood, bark, sap and flowers separately). Commonly known compounds such as 1-hydroxyjunenol, p-hydroxybenzaldehyde, p-methoxybenzoic acid, 3,4,5-trimethoxycinnamyl alcohol, the coumarin scopoletin, the nor-terpenoids 9-dehydrovomifoliol and 2,3-dihydrovomifoliol were obtained. Taspine, two aporphinic alkaloids, the diterpenes 9(11)-dehydrokaurenic acid, hardwikiic acid, the corresponding new 12-oxo derivative as well as five clerodanes and a phorbol ester were also isolated. Three clerodanes were not previously described and their NMR spectroscopical data and MS fragmentation patterns are reported.

Sipandinolide: a butenolide including a novel type of carbon skeleton from Siparuna andina.

From a lipophilic extract of leaves of Siparuna andina (Monimiaceae), which exhibited antiplasmodial activity in vitro, two new compounds have been isolated: sipandinolide (1), a compound with a novel type of carbon skeleton and (-)-cis-3-acetoxy-4',5,7-trihydroxyflavanone (2). Their structures were established by spectroscopic methods; 2 showed moderate antiplasmodial activity whereas 1 was inactive.

Triterpenoid p-aminobenzoates from the seeds of zucchini.

An investigation of the triterpenoid fraction of zucchini seeds afforded two novel multiflorane p-aminobenzoates, identified as 7-epi zucchini factor A and debenzoyl zucchini factor B. Multiflorane p-aminobenzoates could not be detected in zucchini sprouts, which contained bryonolic acid as the only multiflorane constituent. No compound of this type could be obtained from adult plant parts (roots, stems, leaves).

Hyperforin analogues from St. John's wort (Hypericum perforatum).

Three oxygenated analogues of the prenylated phloroglucinol hyperforin (3-5) were isolated from the aerial parts of Hypericum perforatum and their structures elucidated by spectroscopic methods.

Polycyclic diterpenoids from Euphorbia characias.

In addition to widespread flavonoids, a collection of Euphorbia characias from Sardinia afforded 13 oxygenated diterpenoids of the atisane, abietane, pimarane, and kaurane type. Four of these compounds (1, 3a, 7a,b) are new. The accumulation of substantial amounts of biologically active diterpenoids of limited availability, like ent-atisanes endowed with anti-HIV activity and ent-abietanolides active on the central nervous system, makes E. characias an interesting source of lead compounds for biomedical research.

Bonaspectins and neobonaspectins, first sesquilignans and sesquineolignans from a convolvulaceous species.

Four new tetrahydrofuran-type sesquilignans, named bonaspectin A, bonaspectin B, bonaspectin C 4''-beta-glucoside and bonaspectin D 4''-beta-glucoside, as well as two new 8.O.4'-type sesquineolignans, named neobonaspectin A and B, were isolated from the aerial vegetative parts of Bonamia spectabilis (Convolvulaceae), together with the known compound rel-(7S,8S,7'R,8'R)-3,3',4,4',5,5'-hexamethoxy-7.O.7',8.8'-lignan. Their structures were established on the basis of spectral data.

Diterpenoids from euphorbia pithyusa subsp. cupanii

The aerial parts of Euphorbia pithyusa subsp. cupanii collected in Sardinia afforded eleven novel diterpenoids belonging to the lathyrane (1a), premyrsinane (4a-g), and tigliane (5a-c) types. Compounds 4a-g and 5a are esters of two new parent alcohols, named premyrsinol and 4,12,20-trideoxyphorbol, respectively. Structures were elucidated by spectroscopic and chemical methods. Puzzling differences between the NMR data of lathyrol (1c) and its esters were rationalized in terms of flipping of the exomethylene around the mean plane of the macrocycle.

Furohyperforin, a prenylated phloroglucinol from st. John's wort (Hypericumperforatum)

Furohyperforin, an oxygenated analogue of the prenylated phloroglucinol hyperforin, was isolated from the aerial parts of Hypericum perforatum. Its structure was elucidated as 2 on the basis of extensive NMR investigations.

An expeditious procedure for the isolation of ingenol from the seeds of euphorbia lathyris

A short and practical process for the isolation of ingenol (1a) from an agricultural commodity (the seeds of Euphorbia lathyris) is described. Macrocyclic diterpene esters are obtained as byproducts, and the esterification pattern of the Euphorbia factors L2 (3), L3 (4a), and L8 (4b) was established by 2D NMR measurements. Full spectroscopic data for these compounds are reported.

Isoterracinolides A and B, novel bishomoditerpene lactones from euphorbia terracina

An extract of Euphorbia terracina L. has yielded six acylated polyhydroxy terpenoid lactones (1-6), which all display the C22 17-ethyljatrophane carbon framework. Four of these (1-4) are delta lactones belonging to the previously described terracinolide type, and two of them (2, 3) are new. Two further new compounds have been named isoterracinolides A (5) and B (6) and exhibit an eight-membered lactone ring. Another isolated new compound is the jolkinolide-type, ent-abietane gamma lactone (7).

Macrocyclic diterpenoids from Euphorbia semiperfoliata.

In addition to known compounds, the aerial parts of E. semiperfoliata afforded an abietanolide (3), 13 jatrophane polyesters (4-9, 12, 14-19), two 4-deoxyphorbol diesters (23, 24), and a pair of epimeric diterpenes (21, 22) with a novel carbon skeleton, which was named euphoperfoliane. Structures were determined by spectroscopic analysis, and the main conformational features of jatropha-6(17),11-dienes are discussed in detail. The obtained isolation yield of several jatrophanes was unprecedented within the spurges (Euphorbia spp.), making E. semiperfoliata a unique source of macrocyclic diterpenoids.

Structures of the two saponins isolated from commercially available root extract of Primula sp.

The two main saponins of commercially available extract of Primula sp. were isolated by HPLC. Their structures were elucidated by spectroscopic methods as already known primulasaponin (1) and the new 3-O-¿[alpha-rhamnopyranosyl-(1-->2)-beta- galactopyranosyl-(1-->3)-[beta-xylopyranosyl-(1-->4)-beta-glucopyranosyl - (1-->2)]-beta-glucuronopyranosyl]¿-protoprimulagenin A (2).

Sesquiterpene glycosides from Calendula arvensis.

The extract of the aerial parts of Calendula arvensis afforded four new sesquiterpene glycosides 1-4 in addition to three known compounds. The structures of the new compounds were established by high field 1H-nmr spectroscopy.

Acetylenes and Other Constituents from Artemisia dracunculus.

The aerial parts of ARTEMISIA DRACUNCULUS afforded several known compounds as well as three new acetylenes, two phenylpropane derivatives, two monoterpenes, hex-3 Z-en-1-ol and vomifoliol A glucosides. The structures were elucidated by spectroscopic methods and a few chemical transformations.

Aromatic Constituents from Vladimiria souliei.

The polar parts of the title plant gave several lignans including six new ones named vladinol A-F. The structures were elucidated by high field (1)H-NMR spectroscopy and a few chemical reactions. The stereochemistry was determined by the observed NOE's and by comparison of the (1)H-NMR data with those of related lignans.