Synthadotin, ILX-651, BSF-223651, LU-223651
4H-1-苯并吡喃-4-酮,3-溴-6,7-二氯-Chemical Name: N,N-Dimethyl-L-valyl-L-valyl-L-(N-methyl)valyl-L-prolyl-L-proline tert-butylamide hydrochloride
CAS No. 192658-64-3 (free base)
项目整合开发状态: Phase II
项目研究机构: Abbott (Originator), Ilex Oncology (Licensee)
合成路线:The condensation of N-(benzyloxycarbonyl)-N-methyl-L-valine (I) with L-proline methyl ester (II) by means of pivaloyl chloride and triethylamine gives the dipeptide (III),which is deprotected with H2 over Pd/C in methanol yielding N-methyl-L-valyl-L-proline methyl ester (IV).The condensation of (IV) with N-(benzyloxycarbonyl)-L-valine N-carboxyanhydride (V) by means of DIEA in DMG affords the tripeptide (VI),which is deprotected by hydrogenation over Pd/C in methanol giving L-valyl-L-(N-methyl)valyl-L-proline methyl ester (VII).A new condensation of (VII) with (V) yields the tetrapeptide (VIII),which is hydrolyzed with LiOH in methanol affording N-(benzyloxycarbonyl)-L-valyl-L-valyl-L-(N-methyl)valyl-L-proline (IX),which is condensed with L-proline tert-butylamide (X) by means of NMM and EDC in dichloromethane giving the pentapeptide (XI),which is deprotected with H2 over Pd/C in methanol and reductomethylated with formaldehyde and H2 over Pd/C in the same solvent.
📌 参考资料/链接：
参考文献标题:Antineoplastic peptides
文献作者:Amberg,W.; Barlozzari,T.; Bernard,H.; Buschmann,E.; Haupt,A.; Hege,H.-G.; Janssen,B.; Kling,A.; Lietz,H.; Ritter,K.; Ullrich,M.; Weymann,J.; Zierke,T.(BASF AG)
参考来源:JP 2000502092; WO 9722621
📄 详细内容
合成路线:The condensation of N-(benzyloxycarbonyl)-N-methyl-L-valine (I) with L-proline methyl ester (II) by means of pivaloyl chloride and triethylamine gives the dipeptide (III),which is deprotected with H2 over Pd/C in methanol yielding N-methyl-L-valyl-L-proline methyl ester (IV).The condensation of (IV) with N-(benzyloxycarbonyl)-L-valine N-carboxyanhydride (V) by means of DIEA in DMG affords the tripeptide (VI),which is deprotected by hydrogenation over Pd/C in methanol giving L-valyl-L-(N-methyl)valyl-L-proline methyl ester (VII).A new condensation of (VII) with (V) yields the tetrapeptide (VIII),which is hydrolyzed with LiOH in methanol affording N-(benzyloxycarbonyl)-L-valyl-L-valyl-L-(N-methyl)valyl-L-proline (IX),which is condensed with L-proline tert-butylamide (X) by means of NMM and EDC in dichloromethane giving the pentapeptide (XI),which is deprotected with H2 over Pd/C in methanol and reductomethylated with formaldehyde and H2 over Pd/C in the same solvent.
参考文献标题:Dolastatin-15 derivs.in combination with taxanes
文献作者:Barlozzari,T.; Haupt,A.(BASF AG)
参考来源:WO 9840092
产品链接: CAS No. 192658-64-3››