PhTX-56
Chemical Name: N1-[5-(6-Aminohexylamino)pentyl]-N2-butyryl-L-tyrosinamide bis(trifluoroacetate)
CAS No. 401601-08-9, 401601-07-8 (free base)
项目整合开发状态: Biological Testing
项目研究机构: Lundbeck (Originator)
合成路线:The trityl resin derivatized with 1,6-hexanediamine (I) is reacted with 2 nitrobenzenesulfonyl chloride (II) to give the resin-bound sulfonamide (III).Acylation of 5-amino-1-pentanol (V) with 2-(trimethylsilyl)ethyl 4-nitrophenyl carbonate (IV) affords the N-protected aminoalcohol (VI),which is subjected to Mitsunobu coupling with the sulfonamide resin (III) in the presence of 1,1' (azadicarbonyl)dipiperidine (ADDP) and tributylphosphine producing resin (VII).The N-Teoc protecting group of (VII) is selectively removed by means of tetrabutylammonium fluoride to give the amine resin (VIII),which is further coupled to N-Fmoc-O-t-butyl-L-tyrosine (IX) in the presence of HATU and collidine to furnish amide (X).
合成路线:Selective removal of the N-Fmoc group from the fully protected resin (X) by treatment with piperidine in DMF leads to amine (XI),which is then acylated by butyric acid (XII) yielding the butyramide (XIII).The o-nitrobenzenesulfonyl group in (XIII) is then removed with mercaptoethanol and DBU to afford (XIV).Finally,cleavage from the resin and removal of the O-tert-butyl protecting group of (XIV) by means of trifluoroacetic acid and triisopropylsilane provides the title compound.
📌 参考资料/链接：
参考文献标题:Substd.polyamine cpds.
文献作者:Usherwood,P.N.R.; Andersen,K.; Stroemgaard,K.; Jaroszewski,J.W.; Korgsgaard-Larsen,P.; Mellor,I.R.; Egebjerg,J.(H.Lundbeck A/S)
参考来源:WO 0216314
📄 详细内容
合成路线:The trityl resin derivatized with 1,6-hexanediamine (I) is reacted with 2 nitrobenzenesulfonyl chloride (II) to give the resin-bound sulfonamide (III).Acylation of 5-amino-1-pentanol (V) with 2-(trimethylsilyl)ethyl 4-nitrophenyl carbonate (IV) affords the N-protected aminoalcohol (VI),which is subjected to Mitsunobu coupling with the sulfonamide resin (III) in the presence of 1,1' (azadicarbonyl)dipiperidine (ADDP) and tributylphosphine producing resin (VII).The N-Teoc protecting group of (VII) is selectively removed by means of tetrabutylammonium fluoride to give the amine resin (VIII),which is further coupled to N-Fmoc-O-t-butyl-L-tyrosine (IX) in the presence of HATU and collidine to furnish amide (X).
合成路线:Selective removal of the N-Fmoc group from the fully protected resin (X) by treatment with piperidine in DMF leads to amine (XI),which is then acylated by butyric acid (XII) yielding the butyramide (XIII).The o-nitrobenzenesulfonyl group in (XIII) is then removed with mercaptoethanol and DBU to afford (XIV).Finally,cleavage from the resin and removal of the O-tert-butyl protecting group of (XIV) by means of trifluoroacetic acid and triisopropylsilane provides the title compound.
参考文献标题:Solid-phase synthesis of polyamine toxin analogues: Potent and selective antagonists of Ca2+-permeable AMPA receptors
文献作者:Kromann,H.; Krikstolaityte,S.; Andersen,A.J.; Andersen,K.; Krogsgaard-Larsen,P.; Jaroszewski,J.W.; Egebjerg,J.; Stromgaard,K.
参考来源:J Med Chem 2002,45(26),5745
产品链接: CAS No.401601-07-8››