KST-150257

Chemical Name: 7-[2-(2-Aminothiazol-4-yl)-2(Z)-(hydroxyimino)acetamido]-3-[2-(3-chloroisoxazol-5-yl)vinyl]-3-cephem-4-carboxylic acid sodium salt
项目整合开发状态: Preclinical
项目研究机构: Korea Inst. Sci. Technol. (Originator)
合成路线:The cephalosporin was synthesized following the reaction pathway depicted in Scheme 25490101a:Protected 2-(2-aminothiazol-4-yl)-2-(alkoxy)iminoacetic acid ((Ia-c) was reacted with p-methoxybenzyl 7-amino-3-chloromethyl-cephaslosporonate (II) by a conventional method (POCl3,pyr / CH2Cl2.-5 C) to give the acylated product (IIIa-c).Product (IIIa-c) was then coverted to a phosponium salt (Iva-c) (PPh3,NaI / acetone,r.t.),followed by the reaction (NaHCO3(2N) / CH2Cl2,0 C - r.t.) with a substituted isoxazole aldehyde (V) to afford the protected final product (Via-c).The aldehyde (V) was prepared by the sequential reduction-oxidation of the 1,3-dipolar cycloaddition product of methyl propiolate and the corresponding aldoxime.Deprotection,sodium salt formation and purification by reverse phase column chromatography (LiChrosorb(R) RP-18,25% aq.MeOH) followed by frezee drying gave the final product as an amorphous white solid.

合成路线:The cephalosporin was synthesized following the reaction pathway depicted in Scheme 25490201a:Protected 2-(2-aminothiazol-4-yl)-2-(alkoxy)iminoacetic acid ((Ia-c) was reacted with p-methoxybenzyl 7-amino-3-chloromethyl-cephaslosporonate (II) by a conventional method (POCl3,pyr / CH2Cl2.-5 C) to give the acylated product (IIIa-c).Product (IIIa-c) was then coverted to a phosponium salt (Iva-c) (PPh3,NaI / acetone,r.t.),followed by the reaction (NaHCO3(2N) / CH2Cl2,0 C - r.t.) with a substituted isoxazole aldehyde (V) to afford the protected final product (Via-c).The aldehyde (V) was prepared by the sequential reduction-oxidation of the 1,3-dipolar cycloaddition product of methyl propiolate and the corresponding aldoxime.Deprotection,sodium salt formation and purification by reverse phase column chromatography (LiChrosorb(R) RP-18,25% aq.MeOH) followed by frezee drying gave the final product as an amorphous white solid.