Telithromycin, RU-66647, HMR-3647, Levviax, Ketek
泰利霉素 泰利霉素 Chemical Name: 11-Deoxy-3-des(hexopyranosyloxy)-6-O-methyl-3-oxo-N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]amino erythromycin A 11-N,12-O-cyclic carbamate; (3aS,4R,7R,9R,10R,11R,13R,15R,15aR)-4-Ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]-10-[3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyloxy]octahydro-2H-oxacyclotetradecino[4,3-d]oxazole-2,6,8,14(1H,7H,9H)-tetraone
CAS No. 173838-31-8, 191114-48-4 (RU-66647)
项目整合开发状态: Launched-2001
项目研究机构: Aventis Pharma (Originator), Fujisawa (Marketer), Sankyo (Marketer)
合成路线:The selective mesylation of 2'-O-acetyl-3-des(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyloxy)-6-O-methyl-3-oxoerythromycin A (I) with methanesulfonic anhydride in pyridine gives the expected 11-O-methanesulfonyl derivative (II),which is treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in acetone to yield the 10,11-didehydro derivative (III).The acylation of (III) with carbonyl diimidazole (IV) by means of NaH in THF affords the 12-O-acyl derivative (V),which is finally cyclocondensed with 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) in hot acetonitrile.The intermediate compound 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) is obtained as follows: The condensation of N-(4-bromobutyl)phthalimide (VII) with 4-(3-pyridyl)imidazole (VIII) by means of NaH in DMF gives N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]phthalimide (IX),which is then treated with hydrazine in refluxing ethanol.
📌 参考资料/链接：
参考文献标题:Novel erythromycin derivs.,method for their preparation and their use as drugs
文献作者:Agouridas,C.; Chantot,J.-F.; Denis,A.; Gouin d'Ambrieres,S.; Le Martret,O.(Aventis Pharma SA)
参考来源:EP 0680967; FR 2719587; JP 1996053489; JP 1999152296; US 5635485; WO 9529929
📄 详细内容
合成路线:The selective mesylation of 2'-O-acetyl-3-des(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyloxy)-6-O-methyl-3-oxoerythromycin A (I) with methanesulfonic anhydride in pyridine gives the expected 11-O-methanesulfonyl derivative (II),which is treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in acetone to yield the 10,11-didehydro derivative (III).The acylation of (III) with carbonyl diimidazole (IV) by means of NaH in THF affords the 12-O-acyl derivative (V),which is finally cyclocondensed with 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) in hot acetonitrile.The intermediate compound 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) is obtained as follows: The condensation of N-(4-bromobutyl)phthalimide (VII) with 4-(3-pyridyl)imidazole (VIII) by means of NaH in DMF gives N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]phthalimide (IX),which is then treated with hydrazine in refluxing ethanol.
参考文献标题:Novel erythromycin derivs.,their process of preparation and their application as medicines
文献作者:Agouridas,C.; Chantot,J.F.; Denis,A.; Gouin d'Ambrieres,S.; Le Martret,O.(Aventis Pharma SA)
参考来源:FR 2732684
合成路线:The selective mesylation of 2'-O-acetyl-3-des(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyloxy)-6-O-methyl-3-oxoerythromycin A (I) with methanesulfonic anhydride in pyridine gives the expected 11-O-methanesulfonyl derivative (II),which is treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in acetone to yield the 10,11-didehydro derivative (III).The acylation of (III) with carbonyl diimidazole (IV) by means of NaH in THF affords the 12-O-acyl derivative (V),which is finally cyclocondensed with 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) in hot acetonitrile.The intermediate compound 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) is obtained as follows: The condensation of N-(4-bromobutyl)phthalimide (VII) with 4-(3-pyridyl)imidazole (VIII) by means of NaH in DMF gives N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]phthalimide (IX),which is then treated with hydrazine in refluxing ethanol.
参考文献标题:HMR-3647
文献作者:Castar,J.; Graul,A.
参考来源:Drugs Fut 1998,23(6),591
合成路线:The selective mesylation of 2'-O-acetyl-3-des(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyloxy)-6-O-methyl-3-oxoerythromycin A (I) with methanesulfonic anhydride in pyridine gives the expected 11-O-methanesulfonyl derivative (II),which is treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in acetone to yield the 10,11-didehydro derivative (III).The acylation of (III) with carbonyl diimidazole (IV) by means of NaH in THF affords the 12-O-acyl derivative (V),which is finally cyclocondensed with 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) in hot acetonitrile.The intermediate compound 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) is obtained as follows: The condensation of N-(4-bromobutyl)phthalimide (VII) with 4-(3-pyridyl)imidazole (VIII) by means of NaH in DMF gives N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]phthalimide (IX),which is then treated with hydrazine in refluxing ethanol.
参考文献标题:Synthesis and antibacterial activity of HMR 3647 a new ketolide highly potent against erythromycin-resistant and susceptible pathogens
文献作者:Denis,A.; Agouridas,C.; Auger,J.M.; Benedetti,Y.; Bonnefoy,A.; Bretin,F.; Chantot,J.F.; Dussarat,A.; Fromentin,C.; D'Ambrieres,S.G.; Lachaud,S.; Laurin,P.; Le Martret,O.; Loyau,V.; Tessot,N.; Pejac,J.M.; Perron,S.
参考来源:Bioorg Med Chem Lett 1999,9(21),3075
产品链接: CAS No. 173838-31-8›› 产品链接: CAS No.191114-48-4››