【药物名称】PNU-180164
化学结构式(Chemical Structure):
参考文献No.46197
标题:Bicyclic oxazolidinones as antibacterial agent
作者:Hester, J.B. Jr.; Barbachyn, M.R.; Johnson, P.D.; Genin, M.J. (Pharmacia Corp.)
来源:EP 1181288; US 6387896; WO 0073301
合成路线图解说明:

2-Methylindole (I) was nitrated employing NaNO3 in H2SO4 and the resultant 5-nitroindole (II) was further reduced to the corresponding indoline (III) by means of NaBH3CN in the presence of HOAc. Catalytic hydrogenation of the nitro group of (III) over Pd/C furnished diamine (IV), which was converted to the bis-carbamate (V) by treatment with benzyl chloroformate. Oxazolidinone (VII) was then obtained by condensation of carbamate (V) with (R)-glycidyl butyrate (VI) in the presence of BuLi at -78 C. After conversion of alcohol (VII) to the corresponding nosylate (VIII), displacement of its sulfonate group with ammonium hydroxide gave rise to the primary amine (IX). Acetylation of amine (IX), followed by hydrogenolysis of the remaining N-benzyloxycarbonyl group, yielded acetamide (X). The indoline N of (X) was then acylated by acetoxyacetyl chloride (XI) to produce amide (XII). The title compound was then obtained by smooth hydrolysis of the acetoxy group of (XII) with K2CO3, followed by separation of the resultant mixture of diastereoisomers by chiral HPLC.

参考文献No.646183
标题:The potentiating effect of remote chirality on the antibacterial activity of a series of 2-substituted indolinyl phenyloxazolidinones
作者:Genin, M.J.; Barbachyn, M.R.; Grega, K.C.; et al.
来源:41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001,Abst F-1042
合成路线图解说明:

2-Methylindole (I) was nitrated employing NaNO3 in H2SO4 and the resultant 5-nitroindole (II) was further reduced to the corresponding indoline (III) by means of NaBH3CN in the presence of HOAc. Catalytic hydrogenation of the nitro group of (III) over Pd/C furnished diamine (IV), which was converted to the bis-carbamate (V) by treatment with benzyl chloroformate. Oxazolidinone (VII) was then obtained by condensation of carbamate (V) with (R)-glycidyl butyrate (VI) in the presence of BuLi at -78 C. After conversion of alcohol (VII) to the corresponding nosylate (VIII), displacement of its sulfonate group with ammonium hydroxide gave rise to the primary amine (IX). Acetylation of amine (IX), followed by hydrogenolysis of the remaining N-benzyloxycarbonyl group, yielded acetamide (X). The indoline N of (X) was then acylated by acetoxyacetyl chloride (XI) to produce amide (XII). The title compound was then obtained by smooth hydrolysis of the acetoxy group of (XII) with K2CO3, followed by separation of the resultant mixture of diastereoisomers by chiral HPLC.

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