6-O-Methylerythromycin A (I) was converted to a mixture of (E)- and (Z)-oximes upon treatment with hydroxylamine in refluxing MeOH. Beckmann rearrangement of the required (Z)-isomer (II) in the presence of tosyl chloride and NaHCO3 led to the macrocyclic lactam (III). Smooth acidic hydrolysis of (III) selectively removed the 3-cladinose moiety, yielding (IV). The 3-decladinosyl derivative (IV) was then protected as the 2' acetate (V) employing Ac2O in the presence of NaHCO3. Subsequent oxidation of the 3-hydroxyl group of (V) under modified Swern conditions furnished ketone (VI). Finally, methanolysis of the acetate ester group of (VI) provided the title compound.

6-O-Methylerythromycin A (I) was converted to a mixture of (E)- and (Z)-oximes upon treatment with hydroxylamine in refluxing MeOH. Beckmann rearrangement of the required (Z)-isomer (II) in the presence of tosyl chloride and NaHCO3 led to the macrocyclic lactam (III). Smooth acidic hydrolysis of (III) selectively removed the 3-cladinose moiety. The 3-decladinosyl derivative (IV) was then protected as the 2' acetate (V) employing Ac2O in the presence of NaHCO3. Subsequent acylation of the 3-hydroxyl group of (V) with the mixed anhydride prepared from 4-nitrophenylacetic acid (VI) and pivaloyl chloride furnished ester (VII). Finally, methanolysis of the acetate ester group of (VII) provided the title compound.

6-O-Methylerythromycin A (I) was converted to a mixture of (E)- and (Z)-oximes upon treatment with hydroxylamine in refluxing MeOH. Beckmann rearrangement of the required (Z)-isomer (II) in the presence of tosyl chloride and NaHCO3 led to the macrocyclic lactam (III). Smooth acidic hydrolysis of (III) selectively removed the 3-cladinose moiety. The 3-decladinosyl derivative (IV) was then protected as the 2' acetate (V) employing Ac2O in the presence of NaHCO3. Subsequent acylation of the 3-hydroxyl group of (V) with the mixed anhydride prepared from 4-nitrophenylacetic acid (VI) and pivaloyl chloride furnished ester (VII). Finally, methanolysis of the acetate ester group of (VII) provided the title compound.

6-O-Methylerythromycin A (I) was converted to a mixture of (E)- and (Z)-oximes upon treatment with hydroxylamine in refluxing MeOH. Beckmann rearrangement of the required (Z)-isomer (II) in the presence of tosyl chloride and NaHCO3 led to the macrocyclic lactam (III). Smooth acidic hydrolysis of (III) selectively removed the 3-cladinose moiety, yielding (IV). The 3-decladinosyl derivative (IV) was then protected as the 2' acetate (V) employing Ac2O in the presence of NaHCO3. Subsequent oxidation of the 3-hydroxyl group of (V) under modified Swern conditions furnished ketone (VI). Finally, methanolysis of the acetate ester group of (VI) provided the title compound.

6-O-Methylerythromycin A (I) was converted to a mixture of (E)- and (Z)-oximes upon treatment with hydroxylamine in refluxing MeOH. Beckmann rearrangement of the required (Z)-isomer (II) in the presence of tosyl chloride and NaHCO3 led to the macrocyclic lactam (III). Smooth acidic hydrolysis of (III) selectively removed the 3-cladinose moiety. The 3-decladinosyl derivative (IV) was then protected as the 2' acetate (V) employing Ac2O in the presence of NaHCO3. Subsequent acylation of the 3-hydroxyl group of (V) with the mixed anhydride prepared from 4-nitrophenylacetic acid (VI) and pivaloyl chloride furnished ester (VII). Finally, methanolysis of the acetate ester group of (VII) provided the title compound.