HMR-3004, CP-426027, RU-64004, RU-004

Chemical Name: 11,12-(Aminocarbonyloxy)-11,12-dideoxy-3-des(hexopyranosyloxy)-6-O-methyl-3-oxo-N11-[3-(4-quinolyl)propylamino]erythromycin A
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator), Pfizer (Originator)
合成路线:Selective hydrolysis of the cladinose moiety of 6-O-methylerythromycin (I) with aqueous HCl gave (II),which was selectively acetylated at 2'-OH to provide acetate (III).Pfitzner-Moffat oxidation with DMSO,EDC,and pyridinum trifluoroacetate yielded 3-oxo compound (IV).Then,reaction with methanesulfonic anhydride in pyridine gave 11-O-mesylate (V),which on treatment with DBU in acetone produced the elimination product (VI).Subsequent condensation with carbonyldiimidazole in the presence of NaH afforded imidazole-carboxylate (VII).Then,reaction with hydrazine in aqueous acetonitrile provided a mixture of epimeric oxazolidinones (VIII) and (IX),which were separated by column chromatography.

合成路线:Wittig reaction of 4-quinolinecarboxaldehyde (X) with dioxolanylmethyl phosphonium salt (XI) using potassium tert-butoxide in THF produced olefin (XII),which was reduced by catalytic hydrogenation to afford (XIII).Hydrolysis of acetal (XIII) with HCl in acetone-H2O gave quinolinylpropanal (XIV).Finally,reductive alkylation of N-aminoisoxazolone (VIII) with aldehyde (XIV) using NaBH3CN/AcOH in MeOH provided the target compound.