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【结 构 式】 
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【药物名称】TT-24 【化学名称】Mixture of 2-bromo-3-methoxy-6-(methylamino)-1,4,5,8,9,10-hexahydro-9,10[1',2']-benzenoanthracene-1,4,5,8-tetraone and 2-bromo-3-methoxy-7-(methylamino)-1,4,5,8,9,10-hexahydro-9,10[1',2']-benzenoanthracene-1,4,5,8-tetraone 【CA登记号】410087-47-7 (component 1), 410087-46-6 (component 2) 【 分 子 式 】C44H28Br2N2O10 【 分 子 量 】904.52916 |
【开发单位】Kansas State University (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Antimalarials, Oncolytic Drugs, Treatment of Protozoal Diseases, DNA Topoisomerase I Inhibitors, DNA Topoisomerase II Inhibitors, DNA-Damaging Drugs, Drugs Acting on Purine Nucleoside Transporters, Plasmepsin Inhibitors |
合成路线1
Reduction of quinizarin (I) with NaBH4 in MeOH, followed by quenching with HCl provides 1,4-anthraquinone (II). This is further reduced to 1,4-dihydroxyanthracene (III) employing sodium hydrosulfite in dioxane. Subsequent methylation of diol (III) with iodomethane and NaH leads to the key intermediate 1,4-dimethoxyanthracene (IV).
| 【1】 Hua, D.H.; et al.; Syntheses and bioactivities of substituted 9,10-dihydro-9,10[1,2]benzenoanthracene-1,4,5,8-tetrones. Unusual reactivities with amines. J Org Chem 2002, 67, 9, 2907. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 53467 | 1,4-Dihydroxy-9,10-anthracenedione; 1,4-Dihydroxyanthraquinone; Chinizarin; Quinazarin; Quinizarin | 81-64-1 | C14H8O4 | 详情 | 详情 |
| (II) | 53468 | 1,4-Anthracenedione; 1,4-Anthraquinone | 635-12-1 | C14H8O2 | 详情 | 详情 |
| (III) | 53469 | 1,4-anthracenediol | 7218-35-1 | C14H10O2 | 详情 | 详情 |
| (IV) | 53470 | 1,4-dimethoxyanthracene; 4-methoxy-1-anthryl methyl ether | 13076-29-4 | C16H14O2 | 详情 | 详情 |
合成路线2
The Diels-Alder cycloaddition between 1,4-dimethoxyanthracene (IV) and methoxyhydroquinone (V) in the presence of Ag2O and ZnI2 yields the triptycene quinone (VI). This compound has also been obtained by stepwise oxidation of (V) to methoxybenzoquinone (VII) with Ag2O, followed by Diels-Alder condensation with 1,4-dimethoxyanthracene (IV) to produce adduct (VIII) as a mixture of two stereoisomers. After isomerization of ketones (VIII) with KOH, oxidation with Ag2O leads to quinone (VI). Mono-quinone (VI) is oxidized to the bis-quinone (IX) employing ceric ammonium nitrate. Then, regioselective bromination of (IX) with N-bromosuccinimide (NBS) furnishes bromoquinone (X). Alternatively, compound (XI) is obtained from the bromination of (VI) with NBS, followed by oxidation with ceric ammonium nitrate). When bis-quinone (X) in THF solution is treated with dimethylamine gas (containing small amounts of methylamine), the title compound is obtained a regioisomeric mixture of methylamino derivatives, along with the expected dimethylamino analogues, which are separated by column chromatography.
| 【1】 Hua, D.H.; et al.; Syntheses and bioactivities of substituted 9,10-dihydro-9,10[1,2]benzenoanthracene-1,4,5,8-tetrones. Unusual reactivities with amines. J Org Chem 2002, 67, 9, 2907. |
| 【2】 Hua, D.H.; Perchellet, J.-P. (Kansas State University); Triptycene analogs. WO 0228808 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 53470 | 1,4-dimethoxyanthracene; 4-methoxy-1-anthryl methyl ether | 13076-29-4 | C16H14O2 | 详情 | 详情 |
| (V) | 16845 | 2-methoxy-1,4-benzenediol | 824-46-4 | C7H8O3 | 详情 | 详情 |
| (VI) | 53474 | 4,10,13-trimethoxypentacyclo[6.6.6.02,7.09,14.015,20]icosa-2(7),4,9,11,13,15,17,19-octaene-3,6-dione | n/a | C23H18O5 | 详情 | 详情 |
| (VII) | 53471 | Methoxybenzoquinone | 2880-58-2 | C7H6O3 | 详情 | 详情 |
| (VIII) | 53472 | 4,10,13-trimethoxypentacyclo[6.6.6.0~2,7~.0~9,14~.0~15,20~]icosa-4,9,11,13,15,17,19-heptaene-3,6-dione | n/a | C23H20O5 | 详情 | 详情 |
| (IX) | 57853 | 4-methoxypentacyclo[6.6.6.0~2,7~.0~9,14~.0~15,20~]icosa-2(7),4,9(14),11,15,17,19-heptaene-3,6,10,13-tetrone | C21H12O5 | 详情 | 详情 | |
| (X) | 57854 | 4-bromo-5-methoxypentacyclo[6.6.6.0~2,7~.0~9,14~.0~15,20~]icosa-2(7),4,9(14),11,15,17,19-heptaene-3,6,10,13-tetrone | C21H11BrO5 | 详情 | 详情 |