GW-587726X, PL-1441

合成路线: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.

参考文献标题:Novel 8a- and 9a-15-membered lactams
文献作者:Kobrehel,G.; Lazarevski,G.; Alihodzic,S.; Mutak,S.(Pliva dd)
参考来源:EP 1181298; WO 0063223


合成路线: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.

合成路线: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.
参考文献标题:Synthesis and antibacterial activity of isomeric 15-membered azalides
文献作者:Alihodzic,S.; et al.
参考来源:40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000,Toronto) 2001,Abst 1177