Isolation from Euphorbiaceae

The name jatrophane stems from Jatropha gossypiifolia (Euphorbiaceae) whieh was found to contain the antineoplastic and antileukemic (+)-jatrophone. Various differently substituted jatrophanes are isolated from Euphorbiaceae, such as the esulones from Euphorbia esula and the euphomines from E. helioscopia and E. maddeni. 

In regard to the antineoplastic potential, most of the evidence that has emerged from the last 30 years supports the fact that Euphorbiaceae represent a vast reservoir of cytotoxic agents, and one may reasonably expect the isolation of original anticancer agents from this family if enough work is done. A remarkable advance in the study of anticancer principles from Euphorbiaceae has been provided by Wada et al. (34). 

A flavone xylopyranoside, 4, 5-dihyroxy-6,7-dimethoxyflavone-3-0-[3-D-xylopyranoside (155), isolated from the roots of Euphorbia leu-cophylla (family Euphorbiaceae) by Satyanarayana et was found to reduce the blood glucose levels (BGLs) and increase the serum insulin levels in normal and diabetic rats. One flavone [l"(- )-5,4, l"-trihy-droxy-6,7-(3",3"-dimethylchromano)flavone 156] and one flavanone [(25)-4 -0-methyl-6-methyl-8-prenylnaringenin 157) both isolated... 

Naturally Occurring Substances.—Beyeria (Euphorbiaceae) species have been the source of a number of tetracyclic diterpenoids. Some of these were new or poorly defined species and their classification has now been clarified. " The presence of enf-kaurenal has again been recorded in Fusarium monoliforme, whilst ent-kaur-16-en-19-oic acid (72) has been isolated from Mikania hirsutissima (Composi-tae). Microbiological hydro xylation of ent-kaur-16-en-19-oic acid by... 

Two pyridone alkaloids ricinine (238) and nudiflorine (239) have been isolated from Ricinus and TYewia (Euphorbiaceae), respectively (61JBC1186 64CI(L)1524). It has been shown that at least seven species in this family contain enzyme systems that can oxidize 3-cyano-l-methylpyridinium salts in... 

Colubnnol and colubrinol acetate arc isolated from Colubrina texensis Gray (Rhamnaceae) along with maytanbutine. Colubrinol is also isolated from Trewia nudiflora (Euphorbiaceae). The structures for colubrinol and colubrinol acetate were established by high resolution ms and the comparison of tlieir nmr spectra with that of the known maytanbutine. 

Several new alkaloids were isolated at the end of the sixties from Astrocasia phyllanthoides, a shrub belonging to the Euphorbiaceae family and native to Central America.37,38 Astrocasine was proposed as the structure for the predominant alkaloid, based largely on spectral data (IR, UV, NMR, MS) and partial degradation studies. Later, (+)-astrophylline was isolated from the same plant, which is the first natural c/s-cinnamoyl alkaloid to be reported.37... 

A series of proteins, i.e., a-trichosanthin (a-TCS) isolated from the root tubers of Trichosanthes kirilowii, MAP30 isolated from the seeds and fruits of the bitter melon Momordica charantia, GAP31 from Euphorbiaceae himalaya seeds (Gelonium multiflorum), and DAP30 and DAP32 from carnation leaves (Dianthus caryophyllus), have been described to inhibit HIV infection,... 

The boll weevil antifeedants, anthranilic acid, gentisic acid, senecioic acid, trans-cinnamic acid, trans-cinnamaldehyde and camphor have been Isolated from the Peruvian plant Alchornea triplinervia (Euphorbiaceae). Anthranilic acid and camphor also showed significant Inhibition of growth of the tobacco budworm. 

A new skeletal alkaloid, bukittinggine (36), was isolated from Sapium baccatum (Euphorbiaceae). The structure, which is closely related to both methyl homo-secodaphniphyllate (11) and daphnilactone B, was determined by X-ray analysis of its hydrobromide [43]. The presence of bukittinggine indicates that Sapium baccatum may be closely related to the genus Daphniphyllum (Figure 18.5). 

Castaneda P, Garcia MR, Hernandez BE, Torres BA, Anaya AL, Mara R (1992) Effects of Some Compounds Isolated from Celaenodendron mexicanum Standi (Euphorbiaceae) on Seeds and Pathogenic Fungi. J Chem Ecol 18 1025... 

Teuflin, from Teucrium flavum (Labiatae) has been assigned the stereochemistry (39) epimeric at C-10 to teucvidin on the basis of an X-ray analysis. Isocrotocaudin (40) from Croton caudatus (Euphorbiaceae) is an 11(12)-dehydro-derivative which is similar to crotocaudin and teucvidin. The c.d. curves of the a/3-unsaturated lactones have been used to assign the absolute stereochemistry in this series. Plaunol A (41) and plaunol B (42) are anti-ulcer diterpenoid lactones which have been isolated from the Thai medicinal drug Croton sublyratus (Euphorbiaceae). Baccharis genistelloides (Compositae) has afforded a clerodane dilactone (43) similar to that isolated previously from B. trimera. 

Leonurus cardiac (Labiatae) contains some diterpenoids which have been provisionally assigned clerodane structures such as (50). Diasin (51) is a c/5-labdane related to the clerodanes which has been isolated from Croton diasii (Euphorbiaceae). Its structure was determined by and C n.m.r. spectroscopy. A series of furanoid nor-diterpenoids has been isolated from Dioscorea bulbifera (Dioscoreaceae). The structures of the diosbulbins D, E, F, G, and H, (52)—(56), were determined" by a series of spectral and chemical studies and that of diosbulbin G (55) was confirmed" by an X-ray analysis. 

Vemolic acid (or c -12,13-epoxy-octadec-cA-9-enoic acid) (Fig. 6) was the hrst naturally occurring epoxy fatty acid isolated from the seed oil of Vernonia anthelmintica. It is also found in several Compositae, Malvaceae, and Euphorbiaceae species in signihcant amounts. Other epoxy acids include... 

Phorbol and its Relatives.—Jatrophone (114) is a macrocyclic diterpenoid tumour-inhibitor which has been isolated from Jatropha gossypiifolia (Euphorbiaceae). The structure was proven by Z-ray analysis of a cyclization product obtained with HBr in glacial acetic acid. Bertyadional (115) has been isolated from a Bertya species n.m.r. studies defined a large fragment of the molecule. The trienedione, which was reduced with zinc and acetic acid, underwent an isomerization in hot aqueous pyridine in which the 4(10) double bond was shifted to the 1(2) position. 

A number of plant toxins are cyclic members of this series. Huratoxin is the piscicidal constituent of Hura crepitans (Euphorbiaceae). X-Ray analysis showed 34 jjg structure [117 R - H, R = CH CH-CH CH(CH2)8Me] was related to daphnetoxin (117 R = H, R = Ph). Mezerein (117) which is the toxic principle of Daphne mezereum, containsthe cinnamylidene acetic ester (R ) and orthobenzoate (R ) units. Ingenol (118), as its 3-hexadecanoic acid ester, is an irritant isolated from Euphorbia ingens Its structure was determined by X-ray analysis of the triacetate. 

Phorbol (14) was isolated from the oil of Croton tiglium (Euphorbiaceae) seeds " ". The presence of a system containing both the cyclopropanol and the cyclopropylcarbinol functionalities at the C/D ring moiety is quite unusual. Various fatty acid esters of phorbol have been shown to be the active components responsible for the co-carcinogenic activity of croton oil. Esterification usually occurs at C(11) and C(12) with a pair of long chain and short chain fatty acids, as in the potent co-carcinogenic tetradecyl phorbol acetate (TPA). 

Rottlerin (25) is a chromene based on a prenyl-phloroglucinol structure and isolated from the ancient vermifuge drug kamala (Mallotus philippinensis, Euphorbiaceae). It demonstrated efficacy in inhibiting PKC activity competitively with ATP, although the potency varied notably depending on the isoforms. The ICso value was 3 pM for the inhibition of... 

In addition to schweinfurthin C (83), three geranylated stilbenes, schweinfurthins A, B and D (121-123), isolated from Macaranga schweinfurthii (Euphorbiaceae) represent hexahydroxanthene derivatives, which can be considered as substituted cyclized geranylstilbenes [53,72]. 

Epoxylathyrol 5,10-diacetate 3-phenylacetate, which had previously been found in the Euphorbiaceae, has been isolated from Castanopsis lamontii (Fagaceae). 3,12-Di-O-acetylingol 8-tiglate (86) and the 3,5,16,20-tetra-acetate of 16-hydroxyingenol (87) have been isolated - from the irritant latex of Euphorbia lactea. Resiniferatoxin, tinyatoxin (88), and 12-deoxy-4/8-hydroxyphorbol 13-... 

Pborbol and Its Relatives.— The Euphorbiaceae are a rich source of diterpenes. The hydrocarbon casbene (126), which is clearly related to the macrocyclic diterpene cembrene, has been isolated from Ricinus communis It may also be related to the parent hydrocarbon of the phorbol group of diterpenoids. 

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