Valspodar, SDZ-PSC-833, PSC-833, Amdray
伐司扑达Chemical Name: 6-[(2S,4R,6E)-4-Methyl-2-(methylamino)-3-oxo-6-octenoic acid]-7-L-valine-cyclosporin A; Cyclo[[(2S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoyl]-L-valyl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl]
CAS No. 121584-18-7
项目整合开发状态: Phase III
项目研究机构: Novartis (Originator), National Cancer Institute (Codevelopment)
合成路线:By oxidation of cyclosporin D (I) with N-chlorosuccinimide (II) and dimethylsulfide in toluene.
📌 参考资料/链接：
参考文献标题:Cyclosporins and their use as pharmaceuticals
文献作者:Bollinger,P.; B鰈sterli,J.J.; Borel,J.-F.; Krieger,M.; Payne,T.G.; Traber,R.P.; Wenger,R.(Novartis AG)
参考来源:AU 8817679; EP 0296122; JP 1989045396; JP 1996048696; US 5525590
📄 详细内容
合成路线:By oxidation of cyclosporin D (I) with N-chlorosuccinimide (II) and dimethylsulfide in toluene.
参考文献标题:PSC-833
文献作者:Robinson,C.; Castar,J.
参考来源:Drugs Fut 1995,20(10),1010
合成路线:Reaction of the labeled chiral bromoacetylbornanesultam (I) with benzophenone imine (II) and DIEA in hot acetonitrile gives the imine (III),which is enantioselectively alkylated with isopropyl iodide and n-BuLi yielding the L-valine derivative (IV).Treatment of (IV) with HCl in THF in order to eliminate the diphenylmethylene group affords compound (V) with a free amino group that by protection with Boc2O in THF provides the L-valine derivative (VI).The hydrolysis of (VI) with LiOH in THF/water affords labeled N-(tert-butoxycarbonyl)-L-valine (VII),which is condensed with the decapeptide (VIII) by means of BOP and NMM in dichloromethane providing the linear undecapeptide (IX).
合成路线:The reaction of (IX) first with NaOH in ethanol to hydrolyze the terminal ester group,and then with TFA to eliminate the terminal tert-butoxycarbonyl group gives the fully deprotected peptide (X),which is cyclized by means of BOP and NMM in dichloromethane yielding the cyclic peptide (XI).Finally,this compound is oxidized by the modified Pfitzer-Moffat method with DMSO and DCC in tert-butyl methyl ether.
参考文献标题:Synthesis of [S-[1-C-14]Val(7)]VALSPODAR application of (+)/(-)-[C-13,14(N)]BABS and (+)/(-)-[C-13,14(N)]DPMGBS,part 4
文献作者:Metz,Y.; Kohler,B.; Burtscher,P.; Voges,R.; Wenger,R.
参考来源:J Label Compd Radiopharm 2000,43(3),205
产品链接: CAS No. 121584-18-7››