S-23906, S-23906-1
(1R,2R)-REL-1,2-二(乙酰氧基)-1,2,3,14-四氢-6-甲氧基-3,3,14-三甲基-7H-苯并[B]吡喃并[3,2-H]吖啶-7-酮Chemical Name: (?-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
CAS No. 228851-54-5
项目整合开发状态: Preclinical
项目研究机构: Servier (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:Novel acronycine derivs.,preparation method and pharmaceutical compsns.
文献作者:Pfeiffer,B.; Michel,S.; Koch,M.; Pierre,A.; Renard,P.; Tillequin,F.; Atassi,G.(ADIR et Cie.)
参考来源:EP 1042326; FR 2772765; WO 9932491
📄 详细内容
合成路线: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.
参考文献标题:Synthesis and cytotoxic and antitumor activity of benzo[b]pyrano[3,2-h]acridin-7-one analogues of acronycine
文献作者:Costes,N.; Le Deit,H.; Michel,S.; Tillequin,F.; Koch,M.; Pfeiffer,B.; Renard,P.; Leonce,S.; Guilbaud,N.; Kraus-Berthier,L.; Pierre,A.; Atassi,G.
参考来源:J Med Chem 2000,43(12),2395
产品链接: CAS No. 228851-54-5››