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.

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.

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.

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.