- Palladium(II)-catalyzed efficient synthesis of wedelolactone and evaluation as potential tyrosinase inhibitor
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Tyrosinase is an enzyme widely distributed in nature, which has multiple functions, especially in the melanin biosynthesis pathway. Despite the few clinically available tyrosinase inhibitors for whitening, a great demand remains for novel compounds with low side effects in terms of potential carcinogenicity and improved clinical efficacy. A natural product, wedelolactone (WEL), with a polyhydroxyl moiety, attracted our attention as a potential tyrosinase inhibitor. Before we studied the biological activity of the natural product, a synthetic methodological research was firstly carried to obtain enough raw material. WEL could be obtained efficiently through palladium-catalyzed boronation/coupling reactions and 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ)-involved oxidative deprotection/annulation reactions. Immediately after, the natural product was proven to be an efficient tyrosinase inhibitor. In conclusion, we developed a mild and efficient approach for the preparation of WEL, and the natural product was disclosed to have anti-tyrosinase activity, which could be widely used in multiple fields.
- Huang, Huidan,Chen, Jianqiu,Ren, Jie,Zhang, Chaofeng,Ji, Fei
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- Total synthesis of demethylwedelolactone and wedelolactone by Cu-mediated/Pd(0)-catalysis and oxidative-cyclization
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Hedysarimcoumestan B, which can be isolated from Chinese herbal medicine, is achieved, in which the longest linear sequence is only eight steps, in 50% overall yield from commercially available phloroglucinol. The key transformations in the synthesis are Cu-mediated/Pd(0)-catalysis and I2/pyridine oxidative-cyclization reactions. This synthetic strategy can be applied to give access to the demethylwedelolactone (4) and wedelolactone (5), which were afforded from commercially available phloroglucinol in high 38 and 33% yields, respectively.
- Chang, Chia-Fu,Yang, Ling-Yi,Chang, Shiao-Wei,Fang, Yu-Ting,Lee, Yean-Jang
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p. 3661 - 3666
(2008/09/20)
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- Therapeutic drugs for arthritis
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The present invention relates to the coumestans compounds extracted from Compositae plants, drug compositions or health products comprising the compounds and the use in treatment of rheumatic arthritis or rheumatoid arthritis, osteoarthritis. The animal experiments in vivo or in vitro indicate that the coumestans compounds can effectively treat and alleviate symptoms of rheumatic arthritis or rheumatoid arthritis, and osteoarthritis.
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Page/Page column 7
(2008/06/13)
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- Total Synthesis of Wedelolactone
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The total synthesis of wedelolactone, a naturally occurring direct inhibitor of IKK complex that can suppress LPS-induced caspase-11 expression, using a convergent synthetic approach, is described. The key steps involved in this synthesis include the palladium-catalyzed Sonogashira reaction and the palladium-catalyzed carbonylative annulation reaction. This approach allows access to diversified analogues of wedelolactone.
- Li, Chuang Chuang,Xie, Zhi Xiang,Zhang, Yan Dong,Chen, Jia Hua,Yang, Zhen
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p. 8500 - 8504
(2007/10/03)
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- MUSHROOM TYROSINASE CATALYSED SYNTHESIS OF COUMENTANS, BENZOFURAN DERIVATIVES AND RELATED HETEROCYCLIC COMPOUNDS
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Full details of an improved synthesis of coumestan derivatives and their structural analogues, viz., wedelolactone, 11-hydroxy aureol, 11-hydroxy coumestrol along benzofuran derivatives and related heterocyclic systems are reported by coupling of in situ generated o-quinones from catechols catalysed by mushroom tyrosinase with various reatants.
- Pandey, G.,Muralikrishna, C.,Bhalerao, U. T.
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p. 6867 - 6874
(2007/10/02)
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- Wedelolactone and coumestan derivatives as new antihepatotoxic and antiphlogistic principles
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For the study of structure-activity relationships, the antihepatotoxic wedelolactone (7-methoxy-5,11,12-trihydroxy-coumestan) and 6 coumestan derivatives were synthesized by the application of a modified method of Wanzlich. An evaluation of the biological characteristics of the synthetic compounds and acuminatin from Musa acuminata showed that most of the wedelolactone derivatives significantly protected primary cultured liver cells from the toxicity of CCl4, galactosamine (Galc), and phalloidin, and strongly inhibited the activity of 5-lipoxygenase in porcine leukocytes. The hepatocyte protective activity was dependent on the C-7 substitution with pharmacological efficacy decreasing in the following order: EtO > MeO > OH > CH3(CH2)9. In addition, a free OH at C-5 of the wedelolactone molecule was shown to be important in protecting hepatocytes from CCl4 and Galc damage. Similar observation regarding the effect of C-7 substitution in wedelolactone was obtained in the 5-lipoxygenase test. In general, an increase in the lipophilicity in ring A increased the inhibition of 5-lipoxygenase activity. The synthetic wedelolactone was also found to have stimulatory effect on the RNA synthesis in isolated nuclei from hepatocytes.
- Wong,Antus,Gottsegen,Fessler,Rao,Sonnenbichler,Wagner
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p. 661 - 665
(2007/10/02)
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