NSC-708298, DB-67
1H-吡喃o[3',4':6,7]吲哚氮酸[1,2-b]喹啉-3,14(4H,12H)-二酮,11-[(1,1-二甲基乙基)二甲基硅]-4-乙基-4,9-二羟基-, (4S)-Chemical Name: 11-(tert-Butyldimethylsilyl)-4(S)-ethyl-4,9-dihydroxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione; (20S)-7-(tert-Butyldimethylsilyl)-10-hydroxycamptothecin
CAS No. 220913-32-6
项目整合开发状态: Preclinical
项目研究机构: National Cancer Institute (Originator), Tigen Pharmaceuticals (Originator), University of Pittsburgh (Originator), Novartis (Licensee), TaiGen Biotechnology (Codevelopment), TTY Biopharm (Codevelopment)
合成路线:The reaction of the propargyl tetrahydropyranyl ether (I) with TBDMS-Cl and BuLi in THF gives the silylated acetylene (II),which is treated with Br2 and PPh3 to yield the silylated propargyl bromide (III).The reaction of (III) with the pyranopyridone (IV) by means of NaH and LiBr in DMF/DME affords the alkylated pyranopyridone (V),which is cyclized with 4-acetoxyphenyl isocyanide (VI) by means of hexamethyldistannane in refluxing benzene to provide the silylated acetoxycamptothecin (VII).Finally,this compound is deacetylated with K2CO3 in methanol.
📌 参考资料/链接：
参考文献标题:Camptothecin analogs and methods of preparation thereof
文献作者:Bom,D.; Curran,D.P.; Josien,H.(University of Pittsburgh)
参考来源:EP 1017399; JP 2001513567; US 6150343; WO 9909996
📄 详细内容
合成路线:The reaction of the propargyl tetrahydropyranyl ether (I) with TBDMS-Cl and BuLi in THF gives the silylated acetylene (II),which is treated with Br2 and PPh3 to yield the silylated propargyl bromide (III).The reaction of (III) with the pyranopyridone (IV) by means of NaH and LiBr in DMF/DME affords the alkylated pyranopyridone (V),which is cyclized with 4-acetoxyphenyl isocyanide (VI) by means of hexamethyldistannane in refluxing benzene to provide the silylated acetoxycamptothecin (VII).Finally,this compound is deacetylated with K2CO3 in methanol.
参考文献标题:Camptothecin analogs and methods of preparation thereof
文献作者:Bom,D.; Curran,D.P.; Josien,H.; Burke,T.G.(University of Pittsburgh)
参考来源:WO 0035924
合成路线:The reaction of the propargyl tetrahydropyranyl ether (I) with TBDMS-Cl and BuLi in THF gives the silylated acetylene (II),which is treated with Br2 and PPh3 to yield the silylated propargyl bromide (III).The reaction of (III) with the pyranopyridone (IV) by means of NaH and LiBr in DMF/DME affords the alkylated pyranopyridone (V),which is cyclized with 4-acetoxyphenyl isocyanide (VI) by means of hexamethyldistannane in refluxing benzene to provide the silylated acetoxycamptothecin (VII).Finally,this compound is deacetylated with K2CO3 in methanol.
参考文献标题:The novel silatecan 7-tert-butyldimethylsilyl-10-hydroxycamptothecin displays high lipophilicity,improved human blood stability,and potent anticancer activity
文献作者:Bom,D.; Curran,D.P.; Kruszewski,S.; Zimmer,S.G.; Thompson Strode,J.; Kohlhagen,G.; Du,W.; Chavan,A.J.; Fraley,K.A.; Bingcang,A.L.; Latus,L.J.; Pommier,Y.; Burke,T.G.
参考来源:J Med Chem 2000,43(21),3970
合成路线:The reaction of camptothecin (I) with Tbdms-H,(t-BuO)2 and t-BuSH in refluxing dioxane gives the 7-silylcamptothecin (II),which is treated with H2O2 in hot AcOH to give the N-oxide (III).Finally,this compound is isomerized by photolysis in dioxane/H2SO4 to afford the target silylated 10-hydroxycamptothecin.
合成路线:The reaction of 10-hydroxycamptothecin (IV) with Ac2O and pyridine gives the diacetate (V),which is silylated with Tbdms-H,(t-BuO)2 and Tis-SH in refluxing dioxane/TFA to give the silylated diacetate (VI).Finally,this compound is deacetylated by reaction with NaOMe in methanol or HCl in ethanol to afford the target silylated 10-hydroxycamptothecin.
参考文献标题:Semisynthesis of DB-67 and other silatecans from camptothecin by thiol-promoted addition of silyl radicals
文献作者:Du,W.; Kaskar,B.; Blumbergs,P.; Subramanian,P.-K.; Curran,D.P.
参考来源:Bioo.& Med.Chem.2003,11(39),451
产品链接: CAS No. 220913-32-6››