新产品编号:1131639

Chemical Name: (?-(2R*,5Z,9S*,10S*,16R*)-9-Acetoxy-10,2,10-(epoxymetheno)-1-benz[c]azacyclododeca-5-ene-3,7-diyne-1-carboxylic acid 4-chlorophenyl ester,mixture with (2R*,5Z,9R*,10S*,16R*)-isomer (2:1)
项目整合开发状态: Preclinical
项目研究机构: Sanwa (Originator)
合成路线:Treatment of quinoline (I) with ethynylmagnesium bromide (II) in THF at low temperature,and then with 4-chlorophenyl chloroformate (III) gave carbamate (IV).Subsequent deprotection of tert-butyldimethylsilyl group with p-toluenesulfonic acid yielded allyl alcohol (V),and this was stereoselectively epoxidized with m-chloroperbenzoic acid to give epoxyalcohol (VI).Coupling of (VI) with vinyl chloride (VII) in the presence of Pd(0)-CuI catalyst provided the enediyne compound (VIII).This was oxidized with Dess-Martin periodinane reagent to the aldehyde (IX).Finally,CsF-promoted cyclization in the presence of acetic anhydride provided the title compound as a 2:1 mixture of diastereoisomers,which could not be separated.

合成路线:Compound (I) as a 2:1 mixture of diastereoisomers was hydrolyzed with barium hydroxide to afford a mixture of alcohols (II).Further reaction with thiocarbonyldiimidazole (III) and dimethylamino-pyridine (DMAP) gave thiocarbamate (IV),which was finally reduced with tributyltin hydride and azabis(isobutyronitrile) (AIBN) in refluxing benzene.