【药物名称】
化学结构式(Chemical Structure):
参考文献No.13454
标题:1-Azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid cpds.
作者:Murata, M.; Chiba, T.; Tsutsumi, H.; Hattori, K.; Kuroda, S.; Ohtake, H.; Shirai, F. (Fujisawa Pharmaceutical Co., Ltd.)
来源:EP 0394991; JP 1990300187; US 5102877
合成路线图解说明:

Dynamic kinetic resolution of 3-acetyl-1-benzyl-2-pyrrolidinone (I) by Ru-BINAP catalyzed hydrogenation provides the (hydroxyethyl) pyrrolidinone (II). Subsequent reduction of lactam (II) employing NaBH4-BF3旹t2O affords pyrrolidine (III). After debenzylation of (III) by hydrogenation over Pd/C, the resultant pyrrolidine (IV) is protected as the corresponding N-Alloc derivative (V) upon treatment with allyl chloroformate. Subsequent Swern oxidation of the alcohol function of (V) leads to the optically pure ketone (VI). Treatment of ketone (VI) with Me3SiOTf and Et3N, followed by condensation with the acetoxyazetidinone (VII) affords adduct (VIII). Acylation of azetidinone (VIII) with allyl oxalyl chloride (IX), followed by cyclization of the intermediate oxalimide in the presence of triethyl phosphite, gives rise to the carbapenem system ( X). Desilylation of (X) with tetrabutylammonium fluoride leads to alcohol (XI). Further palladium-catalyzed deprotection of both the Alloc and allyl ester groups of (XI) provides the pyrrolidinyl carbapenem (XII). Finally, introduction of the desired N-methyl formimidoyl group into (XII) is accomplished by treatment with ethyl N-methyl formimidate.

参考文献No.664472
标题:Synthesis and antibacterial evaluation of novel 2-[N-imidoylpyrrolidinyl] carbapenems
作者:Hattori, K.; Yamada, A.; Kuroda, S.; Chiba, T.; Murata, M.; Sakane, K.
来源:Bioorg Med Chem Lett 2002,12(3),383
合成路线图解说明:

Dynamic kinetic resolution of 3-acetyl-1-benzyl-2-pyrrolidinone (I) by Ru-BINAP catalyzed hydrogenation provides the (hydroxyethyl) pyrrolidinone (II). Subsequent reduction of lactam (II) employing NaBH4-BF3旹t2O affords pyrrolidine (III). After debenzylation of (III) by hydrogenation over Pd/C, the resultant pyrrolidine (IV) is protected as the corresponding N-Alloc derivative (V) upon treatment with allyl chloroformate. Subsequent Swern oxidation of the alcohol function of (V) leads to the optically pure ketone (VI). Treatment of ketone (VI) with Me3SiOTf and Et3N, followed by condensation with the acetoxyazetidinone (VII) affords adduct (VIII). Acylation of azetidinone (VIII) with allyl oxalyl chloride (IX), followed by cyclization of the intermediate oxalimide in the presence of triethyl phosphite, gives rise to the carbapenem system ( X). Desilylation of (X) with tetrabutylammonium fluoride leads to alcohol (XI). Further palladium-catalyzed deprotection of both the Alloc and allyl ester groups of (XI) provides the pyrrolidinyl carbapenem (XII). Finally, introduction of the desired N-methyl formimidoyl group into (XII) is accomplished by treatment with ethyl N-methyl formimidate.

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