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【结 构 式】 
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【药物名称】S-23906, S-23906-1 【化学名称】(±)-cis-1,2-Bis(acetoxy)-6-methoxy-3,3,14-trimethyl-2,3,7,14-tetrahydro-1H-benzo[b]pyrano[3,2-h]acridin-7-one 【CA登记号】228851-54-5 【 分 子 式 】C28H27NO7 【 分 子 量 】489.52989 |
【开发单位】Servier (Originator) 【药理作用】Antibiotics and Alkaloids, Antineoplastic Antibiotics, Colorectal Cancer Therapy, ONCOLYTIC DRUGS, Apoptosis Inducers, CCNE1 Expression Enhancers, DNA Alkylating Drugs |
合成路线1
The benzoacridine system (III) was obtained by condensation 3-amino-2-naphthalenecarboxylic acid (I) with phloroglucinol (III) in the presence of p-toluenesulfonic acid in refluxing 1-heptanol. Regioselective O-alkylation of (III) with 3-chloro-3-methylbut-1-yne (IV) in DMF at 65 C gave the intermediate propargyl ether (V), which upon further heating at 130 C underwent Claisen rearrangement to produce the pentacyclic compound (VI). Methylation of (VI) with an excess of dimethyl sulfate in the presence of NaH yielded the O,N-dimethyl derivative (VII). The racemic cis diol (VIII) was obtained by OsO4-catalyzed oxidation of (VII) using N-methylmorpholine-N-oxide. Finally, diol (VIII) esterification with Ac2O in pyridine afforded the title diacetate ester.
| 【1】 Michel, S.; Costes, N.; Le Deit, H.; et al.; Synthesis and cytotoxic and antitumor activity of benzo[b]pyrano[3,2-h]acridin-7-one analogues of acronycine. J Med Chem 2000, 43, 12, 2395. |
| 【2】 Pfeiffer, B.; Michel, S.; Koch, M.; Pierre, A.; Renard, P.; Tillequin, F.; Atassi, G. (ADIR et Cie.); Novel acronycine derivs., preparation method and pharmaceutical compsns.. EP 1042326; FR 2772765; WO 9932491 . |
| 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) | 47431 | 3-amino-2-naphthoic acid | 5959-52-4 | C11H9NO2 | 详情 | 详情 |
| (II) | 11799 | 1,3,5-Benzenetriol; Fluoroglucinol | 108-73-6 | C6H6O3 | 详情 | 详情 |
| (III) | 47432 | 1,3-dihydroxybenzo[b]acridin-12(5H)-one | C17H11NO3 | 详情 | 详情 | |
| (IV) | 22416 | 3-chloro-3-methyl-1-butyne | 1111-97-3 | C5H7Cl | 详情 | 详情 |
| (V) | 47433 | 3-[(1,1-dimethyl-2-propynyl)oxy]-1-hydroxybenzo[b]acridin-12(5H)-one | C22H17NO3 | 详情 | 详情 | |
| (VI) | 47434 | 6-hydroxy-3,3-dimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one | C22H17NO3 | 详情 | 详情 | |
| (VII) | 47435 | 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one | C24H21NO3 | 详情 | 详情 | |
| (VIII) | 47436 | (1S,2S)-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one | C24H23NO5 | 详情 | 详情 |