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InChI:InChI=1/C15H16O2/c1-8(2)11-6-5-9(3)13-12(11)7-10(4)14(16)15(13)17/h5-8H,1-4H3

Upstream product

• 2102-75-2 7-hydroxycadalene 
• 125042-09-3 <5,6'-biguaiazulene>-3,3'-(5H,6'H)-dione 
• 123085-55-2 1-(1,5-dimethylhex-4-en-1-yl)-2,3-dimethoxy-4-methylbenzene 

Relevant academic research and scientific papers

Toxicological evaluation of the natural products and some semisynthetic derivatives of Heterotheca inuloides Cass (Asteraceae)

Ethnopharmacological relevance Heterotheca ineuloides Cass (Asteraceae), popularly known as árnica mexicana, is widely used in Mexican traditional medicine to treat bruises, dermatological problems, rheumatic pains, and other disorders as cancer. The major constituents in H. inuloides are cadinane type sesquiterpenes, flavonoids and phytosterols. Compounds with a cadinane skeleton have been proved to possess cytotoxic activity against human-tumor cell lines and brine shrimp, and display toxic effects in different animal species. Although this plant has been widely used, there is little available information on the safety and toxicity especially of pure compounds. Aim of this study Evaluate the potential toxicity of the natural products isolated from H. inuloides and some semisynthetic derivatives. Materials and methods The toxic aspects of the following natural products isolated from dried flowers of H. inuloides: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), (1R,4R)-1-hydroxy-4H-1,2,3,4- tetrahydrocadalen-15-oic acid (4), D-chiro-inositol (5), quercetin (6), quercetin-3,7,3′-trimethyl ether (7), quercetin-3,7,3′,4′-tetramethyl ether (8), eriodictyol-7,4′-dimethyl ether (9), α-spinasterol (10), caryolan-1,9β-diol (11) and 7-(3,3-dimethylallyloxy)-coumarin (12) as well as the toxic aspects of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (13), 7-benzoxy-3,4-dihydrocadalene (14), 7-acetoxycadalene (15), 7-benzoxycadalene (16), quercetin pentaacetate (17), 7-hydroxycalamenene (18), 3,8-dimethyl-5-(1-methylethyl)-1,2-naphthoquinone (19), and 4-isopropyl-1,6-dimethylbenzo[c]oxepine-7,9-dione (20). Toxic activities of compounds were determined by sulforhodamine B (SRB) assay, Artemia salina assay, RAW264.7 macrophage cells. Additionally, the acute toxicity in mouse of compound 1, the major natural sesquiterpene isolated from the acetone extract, was evaluated. Results The best cytotoxicity activity was observed for mansonone C (19) on K562 cell line with IC50 1.45±0.14 μM, for 7-hydroxycadalene (2) on HCT-15 cell line with IC50 18.89±1.2 μM, and for quercetin pentaacetate (17) on MCF-7 cell line with IC50 22.57±2.4 μM. Sesquiterpenes mansonone C (19) and 7-hydroxy-3,4-dihydrocadalene (1) caused the strongest deleterious effects against A. salina with IC50 39.4±1.07, and 45.47±1.74 μM, respectively. The number of viable RAW 264.7 cells was reduced with sesquiterpenes 1 and 2 by more than 90%. In addition, the acute study of 1 revealed no lethal effects at 300 mg/kg body weight, however, a reduction in the body weight of mice, morphological changes in the tissues of the liver and kidney and toxic signs were observed at very high doses (2000 mg/kg). Conclusion The results provided evidence for the cytotoxicity of Mexican arnica (H. inuloides) metabolites and may be correlated with one of the popular uses of this plant, in traditional Mexican medicine, as anticancer remedy. Among the active compounds contained in the acetone extract, the cytotoxic activity is mainly ascribable to cadinene type sesquiterpenes. In addition, evidence of acute toxicity suggests that 7-hydroxy-3,4-dihydrocadalene (1) may lead to toxicity at very high doses.

FORMATION OF THE ORTHO-QUINONE MANSONONE C FROM 7-HYDROXYCADALENE ON SILICS GEL

The sesquiterpene β-naphthol, 7-hydroxycadalene, found inter alia in the heartwood of a number of Ulmus spp., undergoes oxidation on silica gel to mansonone C, one of several related sesquiterpene ortho-quinones produced in some Ulmus spp. in response to certain stresses.The reaction, which appears to involve oxygen adsorbed on the silica gel, proceeds under an argon atmosphere and is dramatically retarded in the absence of light.Key Word Index - Mansonia altissima; Sterculiaceae; Ulmus americana; Ulmaceae; mansonone C; ortho-quinone; 7-hydroxycadalene; oxidation; silica gel.

Use of allylic strain to enforce stereochemistry. Direct syntheses of 7,8-dihydroxycalamenene and mansonone C

Direct syntheses of 7,8-dihydroxycalamenene and mansonone C were achieved. The cis-stereochemistry required for the synthesis of 7,8-dihydroxycalamenene was introduced by an intramolecular cyclization directed by allylic strain.

An Efficient Preparation and Reactions of -3,3'(5H,6'H)-dione and 5-Isopropylidene-3,8-dimethyl-1(5H)-azulenone: Key Intermediates for the Autoxidation Products of Guaiazulene

Oxidation of guaiazulene (1) with peracetic acid in hexane at 25 deg C afforded as high as an 80percent yield of the title biguaiazulenedione (12), which upon heating at 60 deg C under nitrogen gave the title 1-azulenone (13) quantitatively.Oxidation of 12 and 13 was studied under various conditions, and these compounds were shown to be highly important key intermediates for a large number of the complex products obtained by autoxidation of 1.