新产品编号:1704323

合成路线:Silylation of carboxylic acid (I) by means of tert-butyldimethylsilyl chloride and imidazole in DMF yields derivative (II),which then reacts with allyl glyoxylate (III) in toluene to afford (IV).Treatment of (IV) with SOCl2 and pyridine in THF provides chloro azetidinone (V),which is then converted into (VI) by means of PPh3 and pyridine or 2,6-lutidine in DMF.Ylide acid (VI) is treated with 2-pyridyl chlorothioformate (VII) and Et3N in CH2Cl2 to give derivative (VIII),which is then condensed with the Grignard reagent (XI) and desilylated by means of H2SO4 in MeOH to provide ketophosphorane (XII).Cyclization of (XII) via an internal Wittig reaction by treatment with refluxing p-xylene gives carbapenem (XIII),which is then converted into the corresponding iodide (XIV) via mesylation with MsCl by means of TEA in dichloromethane followed by Finkelstein reaction with NaI in acetone.Reaction of (XIV) with 2-aminopyridine (XV) in acetonitrile provides pyridinium salt (XVI),whose allyl protecting groups are removed by treatment with Pd(PPh3)4,PPh3 in CH2Cl2/EtOAc,followed by 2-ethylhexanoic acid and potassium 2-ethylhexanoate in EtOAc.

合成路线:Reagent (XI) can be prepared as follows: Reduction of carboxylic acid (IX) with LiAlH4 in Et2O or BH3 in THF followed by alcohol protection with TBDMSCl in CH2Cl2 in the presence of TEA and DMAP yields silyl ether (X).Derivative (X) is finally converted into Grignard reagent (XI) by means of Mg in THF or,alternatively,by treatment with t-BuLi in THF followed by MgBr2 in CH2Cl2 in the presence of TEA.

参考文献标题:2-Naphthylcarbapenems: Broad spectrum antibiotics with enhanced potency against MRSA
文献作者:Greenlee,M.L.; DiNinno,F.; Herrmann,J.J.; Jaworsky,C.; Muthard,D.A.; Salzmann,T.N.
参考来源:Bioorg Med Chem Lett 1999,9(19),2893


合成路线:Silylation of carboxylic acid (I) by means of tert-butyldimethylsilyl chloride and imidazole in DMF yields derivative (II),which then reacts with allyl glyoxylate (III) in toluene to afford (IV).Treatment of (IV) with SOCl2 and pyridine in THF provides chloro azetidinone (V),which is then converted into (VI) by means of PPh3 and pyridine or 2,6-lutidine in DMF.Ylide acid (VI) is treated with 2-pyridyl chlorothioformate (VII) and Et3N in CH2Cl2 to give derivative (VIII),which is then condensed with the Grignard reagent (XI) and desilylated by means of H2SO4 in MeOH to provide ketophosphorane (XII).Cyclization of (XII) via an internal Wittig reaction by treatment with refluxing p-xylene gives carbapenem (XIII),which is then converted into the corresponding iodide (XIV) via mesylation with MsCl by means of TEA in dichloromethane followed by Finkelstein reaction with NaI in acetone.Reaction of (XIV) with 2-aminopyridine (XV) in acetonitrile provides pyridinium salt (XVI),whose allyl protecting groups are removed by treatment with Pd(PPh3)4,PPh3 in CH2Cl2/EtOAc,followed by 2-ethylhexanoic acid and potassium 2-ethylhexanoate in EtOAc.
参考文献标题:Structure-activity relationships in the 2-arylcarbapenem series: Synthesis of 1-methyl-2-arylcarbapenems
文献作者:Guthikonda,R.N.; Cama,L.D.; Quesada,M.; Woods,M.F.; Salzmann,T.N.; Christensen,B.G.
参考来源:J Med Chem 1987,30(5),871