新产品编号:187185
Chemical Name: (4S,5R,6R)-4-Amino-6-[N-(2-phenylethyl)-N-propylcarbamoyl]-5-(trifluoroacetamido)-5,6-dihydro-4H-pyran-2-carboxylic acid
CAS No. 185381-95-7
项目整合开发状态: Preclinical
项目研究机构: Biota Scientific Management (Originator)
合成路线:Introduction of a Boc protecting group on derivative (I) by treatment with tert-butyldicarbonate and DMAP in dioxane affords 5-N-Boc derivative (II),which is then deacetylated by reaction with NaOMe in MeOH to provide compound (III).Conversion of trihydroxy derivative (III) into carboxylic acid (IV) is performed by first oxidation with sodium periodate in MeOH/H2O followed by treatment with sodium chlorite/potassium dihydrogen orthophosphate in tert-BuOH.Coupling of (IV) with secondary amine (V) by means of TBTU in THF yields phenethylpropyl carbamoyl derivative (VI),whose Boc group is removed by means of HCl in dioxane to give primary amine (VII).Condensation of (VII) with trifluoroacetic anhydride (VIII) in pyridine furnishes trifluoroacetylamino derivative (IX),whose azide group is reduced by means of PPh3 and Et3N in THF/H2O to yield 4-amino derivative (X).Finally,the desired product is obtained by saponification of the methyl ester group of (X) by heating with Et3N in H2O.
📌 参考资料/链接：
参考文献标题:6-Carboxamido dihydropyran derivs.
文献作者:Smith,P.; Sollis,S.; Cherry,P.; Howes,P.(Biota Scientific Management Pty Ltd.)
参考来源:US 5990156; WO 9636628
📄 详细内容
合成路线:Introduction of a Boc protecting group on derivative (I) by treatment with tert-butyldicarbonate and DMAP in dioxane affords 5-N-Boc derivative (II),which is then deacetylated by reaction with NaOMe in MeOH to provide compound (III).Conversion of trihydroxy derivative (III) into carboxylic acid (IV) is performed by first oxidation with sodium periodate in MeOH/H2O followed by treatment with sodium chlorite/potassium dihydrogen orthophosphate in tert-BuOH.Coupling of (IV) with secondary amine (V) by means of TBTU in THF yields phenethylpropyl carbamoyl derivative (VI),whose Boc group is removed by means of HCl in dioxane to give primary amine (VII).Condensation of (VII) with trifluoroacetic anhydride (VIII) in pyridine furnishes trifluoroacetylamino derivative (IX),whose azide group is reduced by means of PPh3 and Et3N in THF/H2O to yield 4-amino derivative (X).Finally,the desired product is obtained by saponification of the methyl ester group of (X) by heating with Et3N in H2O.
参考文献标题:Sialidase inhibitors related to zanamivir.Further SAR studies of 4-amino-4H-pyran-2-carboxylic acid-6-propylamides
文献作者:Wyatt,P.G.; Coomber,B.A.; Evans,D.N.; Jack,T.I.; Fulton,H.E.; Wonacott,A.J.; Colman,P.; Varghese,J.
参考来源:Bioorg Med Chem Lett 2001,11(5),669
合成路线:Introduction of a Boc protecting group on derivative (I) by treatment with tert-butyldicarbonate and DMAP in dioxane affords 5-N-Boc derivative (II),which is then deacetylated by reaction with NaOMe in MeOH to provide compound (III).Conversion of trihydroxy derivative (III) into carboxylic acid (IV) is performed by first oxidation with sodium periodate in MeOH/H2O followed by treatment with sodium chlorite/potassium dihydrogen orthophosphate in tert-BuOH.Coupling of (IV) with secondary amine (V) by means of TBTU in THF yields phenethylpropyl carbamoyl derivative (VI),whose Boc group is removed by means of HCl in dioxane to give primary amine (VII).Condensation of (VII) with trifluoroacetic anhydride (VIII) in pyridine furnishes trifluoroacetylamino derivative (IX),whose azide group is reduced by means of PPh3 and Et3N in THF/H2O to yield 4-amino derivative (X).Finally,the desired product is obtained by saponification of the methyl ester group of (X) by heating with Et3N in H2O.
参考文献标题:Synthesis and influenza virus sialidase inhibitory activity of analogues of 4-guanidino-Neu5Ac2en (GG167) with modified 5-substituents
文献作者:Smith,P.W.; et al.
参考来源:Eur J Med Chem 1996,31(2),143