药物详细合成路线
| Name | (-)-Epigallocatechin gallate;(-)-EGCG | | Chemical Name | 3,4,5-Trihydroxybenzoic acid (2R-cis)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3-yl ester
(-)-Epigallocatechin 3-O-gallate
(-)-3-O-Galloylepigallocatechin | | CAS | 989-51-5 | | Related CAS | | | Formula | C22H18O11 | | Structure |  | | Formula Weight | 458.38216 | | Stage | III 期临床 | | Company | National Cancer Institute (Not Determined), University of California, San Francisco (Not Determined) | | Activity/Mechanism | Actinic Keratoses, Agents for, Agents for Liver Fibrosis, Chemopreventive Agents, Dermatologic Drugs, GASTROINTESTINAL DRUGS, Liver and Biliary Tract Disorders, Treatment of, ONCOLYTIC DRUGS, Angiogenesis Inhibitors, Antioxidants, AP-1 Inhibitors, beta-Secretase (BACE) Inhibitors, Fatty Acid Synthase Inhibitors, NF-kappaB (NFKB) Activation Inhibitors, PDGFR Inhibitors, Telomerase Inhibitors, VEGFR Inhibitors, VEGFR-2 (FLK-1/KDR) Inhibitors | | Syn. Route | 1 | | Route 1 | | an enantioselective synthesis of epigallocatechin-3-gallate has been reported: the condensation of 3,4,5-tris(benzyloxy)cinnamyl alcohol (i) with 3,5-bis(benzyloxy)phenol (ii) by means of h2so4 gives the diphenylpropene derivative (iii), which is silylated with tbdms-cl and imidazole to yield the silyl ether (iv). the asymmetric dihydroxylation of (iv) with ad-mix-alpha affords diol (v), which is desilylated with tbaf in thf providing the trihydroxy compound (vi). esterification of (vi) with triethyl orthoformate and pyridinium p-toluenesulfonate (ppts) at room temperature gives the cyclic orthoester (vii), which is treated with the same reactants at 60 °c to yield the benzopyran (viii). compound (viii) can also be obtained directly from (vi) by treatment with triethyl orthoformate and ppts at 60 °c. the hydrolysis of the formate group of (viii) with k2co3 in methanol affords alcohol (ix), which is oxidized to the corresponding ketone (x) with dess-martin periodinane (dmp) in dichloromethane. the reduction of (x) with l-selectride in thf provides the chiral cis-alcohol (xi), which is esterified with 3,4,5-tris(benzyloxy)benzoyl chloride (xii) and dmap in dichloromethane giving rise to the protected ester (xiii). finally, this compound is debenzylated by hydrogenation with h2 over pd/c in methanol/thf. | | |  | | List of intermediates | No. | | tert-butyl 4-(tributylstannyl)-3,6-dihydro-1(2h)-pyridinecarboxylate | (xii) | | 2-(2,6-dichlorophenyl)-2-(6-methyl-3-pyridazinyl)acetonitrile | (i) | | 2,4-difluorobenzenethiol; 2,4-difluorophenylhydrosulfide | (ii) | | 2-(2,6-dichlorophenyl)-2-{6-[(2,4-difluorophenyl)sulfanyl]-3-pyridazinyl}acetonitrile | (iii) | | 2-(2,6-dichlorophenyl)-2-{6-[(2,4-difluorophenyl)sulfanyl]-3-pyridazinyl}acetamide | (iv) | | | (v) | | ethyl 2-{[tert-butyl(diphenyl)silyl]oxy}acetate | (vi) | | 1-({[tert-butyl(diphenyl)silyl]oxy}methyl)cyclopropanol | (vii) | | diisopropyl bromomethylphosphonate | (viii) | | diisopropyl {[1-({[tert-butyl(diphenyl)silyl]oxy}methyl)cyclopropyl]oxy}methylphosphonate | (ix) | | diisopropyl {[1-(hydroxymethyl)cyclopropyl]oxy}methylphosphonate | (x) | | {1-[(diisopropoxyphosphoryl)methoxy]cyclopropyl}methyl methanesulfonate | (xi) | | 4-chloro-1h-benzimidazol-6-amine; 4-chloro-1h-benzimidazol-6-ylamine | (xiii) | | | Reference 1: chan, t.h.; li, l.; enantioselective synthesis of epigallocatechin-3-gallate (egcg), the active polyphenol component from green tea. org lett 2001, 3, 5, 739. |
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来源:药化网
作者:药化小编
摘要:本文合成路线介绍的是药物中文名(-)-表没食子儿茶素没食子酸酯；英文名(-)-Epigallocatechin gallate;(-)-EGCG；CAS[989-51-5]
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