Gantacurium chloride, AV-430A, GW-0430, GW-280430A
Chemical Name: (Z)-2-Chlorofumaric acid 1-[3-[6,7-dimethoxy-2(S)-methyl-1(R)-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinolinium-2-yl]propyl] 4-[3-[6,7-dimethoxy-2(R)-methyl-1(S)-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinolinium-2-yl]propyl] diester dichloride
CAS No. 213998-45-9
项目整合开发状态: Phase I
项目研究机构: Avera Pharmaceuticals (Proprietary), Cornell Research Foundation (Originator), GlaxoSmithKline (Originator)
合成路线:Treatment of chlorofumaryl chloride (III) with a mixture of benzylisoquinolinium salt (I) and phenylisoquinolinium salt (II) in dichloroethane produced a complex mixture of esters,from which the title compound was isolated by preparative HPLC.
📌 参考资料/链接：
参考文献标题:Bis- and mixed-tetrahydroisoquinolinium chlorofumarates: New ultra-short-acting nondepolarizing neuromuscular blockers
文献作者:Boros,E.E.; Bigham,E.C.; Boswell,G.E.; Mook,R.A.Jr.; Patel,S.S.; Savarese,J.J.; Ray,J.A.; Thompson,J.B.; Hashim,M.A.; Wisowaty,J.C.; Feldman,P.L.; Samano,V.
参考来源:J Med Chem 1999,42(2),206
📄 详细内容
合成路线:The reaction of (R)-(-)-5'-methoxylaudanosine (I) with 1,3-dioxa-2-thiane 2,2-dioxide (II) in hot acetone gives the quaternized propylsulfonate (III),which is treated with Ac-Cl in methanol to yield the intermediate isoquinolinium derivative (IV).
合成路线:The reaction of (S)(+)-cryptostyline III (V) with 1,3-dioxa-2-thiane 2,2-dioxide (II) in hot acetonitrile gives the quaternized propylsulfonate (VI),which is treated with Ac-Cl in methanol to yield the intermediate isoquinolinium derivative (VII).
合成路线:The reaction of 2,3-dichlorosuccinic anhydride (VIII) with isoquinolinium intermediate (IV) in dichloromethane gives the dichlorosuccinc acid monoester (IX),which is dehydrochlorinated by means of TEA in dichloromethane to yield the chlorofumaric acid monoester (X).The reaction of (X) with oxalyl chloride in the same solvent affords the acyl chloride (XI),which is finally condensed with the isoquinolinium intermediate (VII) in dichloromethane to provide the target bis isoquinolinium compound.
参考文献标题:Synthesis of ultra-short-acting neuromuscular blocker GW 0430: A remarkably stereo- and regioselective synthesis of mixed tetrahydroisquinolinium chlorofumarates
文献作者:Samano,V.; Ray,J.A.; Thompson,J.B.; Mook,R.A.Jr.; Jung,D.K.; Koble,C.S.; Martin,M.T.; Bigham,E.C.; Regitz,C.S.; Feldman,P.L.; Boros,E.E.
参考来源:Org Lett 1999,1(12),1993