新产品编号:595341

Chemical Name: 11-Deoxy-13-des(ethyl)-3-des(hexopyranosyloxy)-13-methyl-6-O-methyl-3-oxo-11-[4-(4-quinolinyl)butylamino]erythromycin A 11-N,12-O-cyclic carbamate
CAS No. 229319-05-5
项目整合开发状态: Preclinical
项目研究机构: Kosan (Originator), R.W. Johnson (Originator)
合成路线:Treatment of erythromycin derivative (I) with hydroxylamine in isopropanol in the presence of HOAc affords oxime (II),which is then converted into the isopropoxycyclohexyl oxime form (IV) by reaction with 1,1-diisopropoxycyclohexane (III) and p-toluensulfonate (PPTS) in CH2Cl2.Regioselective protection of (IV) by means of N-(trimethylsilyl)-imidazole (Me3Si-Im) and chlorotrimethylsilane (TMSCl) in CH2Cl2 yields derivative (V),which is then converted into derivative (VI) by first methylation with methyl bromide and KOtBu in THF/methyl sulfoxide followed by deprotection with HOAc in acetonitrile.Oxime (VI) is then treated with sodium hydrosulfite (Na2S2O4) and formic acid in EtOH/H2O to provide derivative (VII).

合成路线:Acidolysis of (VII) with HCl furnishes des(hexopyranosyloxy) derivative (VIII),which is then acetylated with acetic anhydride in ethyl acetate to give protected derivative (IX).Compound (IX) is then oxidized by treatment with 3-ethylcarbodiimide (EDCI) and pyridinium trifluoroacetate in DMSO/CH2Cl2 to afford ketone (X).Mesylation of (X) with methanesulfonyl chloride (MsCl) in pyridine yields mesylated derivative (XI),which is then converted into the 10,11-anhydro form (XII) by reaction with 1,8-Diazabicyclo(5.4.0)undec-7-ene (DBU) in acetone.Activation of compound (XII) by means of NaH and carbonyl diimidazole (CDI) in THF/DMF provides derivative (XIII),which is coupled with amine (XIV).Finally,treatment with refluxing MeOH furnishes the desired compound.