【药物名称】
化学结构式(Chemical Structure):
参考文献No.55941
标题:6-O-Carbamoyl ketolide derivs. of erythromycin useful as antibacterials
作者:Henninger, T.C.; Xu, X.C. (Ortho-McNeil Pharmaceutical, Inc.)
来源:US 6472372; WO 0246204
合成路线图解说明:

The intermediate aldehyde (VII) has been obtained as follows: The cyclization of 2-fluoro-4-hydrazinobenzonitrile (I) with malonaldehyde (II) by means of HCl in refluxing ethanol gives 2-fluoro-4-(1-pyrazolyl)benzonitrile (III), which is reduced by means of diisobutylaluminum hydride in toluene to yield the benzaldehyde (IV). The condensation of (IV) with (1,3-dioxolan-2-ylmethyl)triphenylphosphonium bromide (V) by means of TDA-1 and K2CO3 in refluxing dichloromethane to afford the 3-[2-fluoro-4-(1-pyrazolyl)phenyl]-2-propenal ethylene ketal (VI), which is finally hydrolyzed with HCl in THF to provide the target intermediate aldehyde (VII).

合成路线图解说明:

The reaction of erythromycin A (VIII) with Ac2O, TEA and DMAP in dichloromethane gives the triacetate (IX), which is treated with NaHMDS in THF to yield the unsaturated erythromycin derivative (X). The treatment of (X) with trichloroacetyl isocyanate (XI), followed by reaction with TEA and t-BuOK affords the cyclic carbamate (XII). The acylation of the 2'-OH of (XII) with Ac2O and TEA, followed by cleavage of its cladinose sugar by means of HCl in ethanol/water provides compound (XIII), which is oxidized and deacetylated to give the ketolide derivative (XIV). Finally, this compound is reductocondensed with the intermediate aldehyde (VII) by means of Tes-H and TFA in acetonitrile to yield the target substituted ketolide.

参考文献No.694584
标题:Synthesis and antibacterial activity of C6-carbamate ketolides
作者:Henninger, T.; et al.
来源:42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002,Abst F-1661
合成路线图解说明:

The reaction of erythromycin A (VIII) with Ac2O, TEA and DMAP in dichloromethane gives the triacetate (IX), which is treated with NaHMDS in THF to yield the unsaturated erythromycin derivative (X). The treatment of (X) with trichloroacetyl isocyanate (XI), followed by reaction with TEA and t-BuOK affords the cyclic carbamate (XII). The acylation of the 2'-OH of (XII) with Ac2O and TEA, followed by cleavage of its cladinose sugar by means of HCl in ethanol/water provides compound (XIII), which is oxidized and deacetylated to give the ketolide derivative (XIV). Finally, this compound is reductocondensed with the intermediate aldehyde (VII) by means of Tes-H and TFA in acetonitrile to yield the target substituted ketolide.

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