FMA-122

Chemical Name: 3-Des(hexopyranosyl)-9-deoxo-9(S)-hydroxy-3-O-[2-(3-pyridyl)acetyl]erythromycin A 6-O,9-O:11-O,12-O-bis(cyclic carbonate)
CAS No. 205320-30-5
项目整合开发状态: Preclinical
项目研究机构: Taisho (Originator)
合成路线:The intermediate dicyclic carbonate (VI) was prepared by two alternative procedures:Erythromycin A (I) was converted into 11,12-cyclic carbonate (II) upon treatment with ethylene carbonate (II).Reduction of (II) with NaBH4 afforded the 9-dihydroerythromicyn derivative (III),which was protected at the 2'-hydroxyl group of the cladinose moiety by acetylation with Ac2O in acetone.Conversion of the resulting acetylated compound (V) to the corresponding 6,9;11,12-dicyclic carbonate was achieved by reaction with either diphosgene or triphosgene in the presence of pyridine,and the subsequent hydrolysis of the 2'-acetate in MeOH at room temperature furnished intermediate (VI).In a shorter procedure,2'-O-acetyl-9-dihydroerythromycin A (VII) was reacted with 1,1'-carbonyldiimidazole and NaH to give the corresponding dicyclic carbonate.The acetate ester was then hydrolyzed to (VI) by treatment with MeOH.

合成路线:Removal of the desosamine unit was effected by hydrolysis in 1N HCl at r.t.The resulting diol (VIII) was then selectively acetylated at the 2'-hydroxyl yielding monoacetate ester (IX).Further coupling of (IX) with 3-pyridylacetic acid-HCl (X) was carried out by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) or,alternatively,by previous activation of (X) as the mixed anhydride with pivalic acid to furnish the 3-O-pyridylacetyl ester (XI).The protecting acetate group of (XI) was finally removed by selective hydrolysis in boiling MeOH.