合成路线:4-Methyl-5-nitroimidazole (I) is condensed with benzaldehyde (II) in the presence of piperidine to produce the 4-styryl imidazole (III).Alkylation of imidazole (III) with benzyl chloride leads to a 3:1 mixture of regioisomeric N-benzyl imidazoles (IV) and (V).Ozonolysis of this mixture,followed by oxidative work-up of the ozonide with performic acid,allows isolation of the desired imidazolecarboxylic acid (VI) by employing a differential precipitation technique.Activation of acid (VI) with CDI,and further treatment of the resultant imidazolide with potassium methanenitronate gives rise to nitro ketone (VII).Both nitro groups of (VII) are then reduced by SnCl2 in concentrated HCl to furnish diamine (VIII).Then,removal of the N-benzyl group of (VIII) by catalytic hydrogenation over Pd/C yields imidazole (IX).Ring closure of (IX) in the presence of triethyl orthoformate produces the imidazodiazepinone (X)
合成路线:After silylation of the imidazodiazepinone (X) employing bis(trimethylsilyl)trifluoroacetamide,glycosylation with 2-deoxy-3,5-di-p-toluoyl-D-erythro-pentofuranosyl chloride (XI) leads to a mixture of glycoside anomers (XII) and (XIII),from which the desired beta-anomer (XII) can be isolated by either column chromatography or by fractional crystallization.The toluoyl ester groups of (XII) are then removed by methanolysis in the presence of NaOMe to afford (XIV).Finally,reduction of ketone (XIV) gives rise to a 60:40 mixture of the target (R)-hydroxy imidazodiazepine along with its (S)-epimer (XV),which are separated by reverse-phase preparative HPLC
参考文献标题:Imidazole cpds.,methods for their production and conversion of said cpds.into (R)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazol[4,5-d][1,3]diazepin-8-ol
文献作者:Baker,D.C.; Putt,S.R.(Pfizer Inc.)
参考来源:US 4195176
合成路线:4-Methyl-5-nitroimidazole (I) is condensed with benzaldehyde (II) in the presence of piperidine to produce the 4-styryl imidazole (III).Alkylation of imidazole (III) with benzyl chloride leads to a 3:1 mixture of regioisomeric N-benzyl imidazoles (IV) and (V).Ozonolysis of this mixture,followed by oxidative work-up of the ozonide with performic acid,allows isolation of the desired imidazolecarboxylic acid (VI) by employing a differential precipitation technique.Activation of acid (VI) with CDI,and further treatment of the resultant imidazolide with potassium methanenitronate gives rise to nitro ketone (VII).Both nitro groups of (VII) are then reduced by SnCl2 in concentrated HCl to furnish diamine (VIII).Then,removal of the N-benzyl group of (VIII) by catalytic hydrogenation over Pd/C yields imidazole (IX).Ring closure of (IX) in the presence of triethyl orthoformate produces the imidazodiazepinone (X)
合成路线:After silylation of the imidazodiazepinone (X) employing bis(trimethylsilyl)trifluoroacetamide,glycosylation with 2-deoxy-3,5-di-p-toluoyl-D-erythro-pentofuranosyl chloride (XI) leads to a mixture of glycoside anomers (XII) and (XIII),from which the desired beta-anomer (XII) can be isolated by either column chromatography or by fractional crystallization.The toluoyl ester groups of (XII) are then removed by methanolysis in the presence of NaOMe to afford (XIV).Finally,reduction of ketone (XIV) gives rise to a 60:40 mixture of the target (R)-hydroxy imidazodiazepine along with its (S)-epimer (XV),which are separated by reverse-phase preparative HPLC
参考文献标题:A total synthesis of pentostatin,the potent inhibitor of adenosine deaminase
文献作者:Baker,D.C.; Putt,S.R.
参考来源:J Am Chem Soc 1979,101(20),6127
合成路线:4-Methyl-5-nitroimidazole (I) is condensed with benzaldehyde (II) in the presence of piperidine to produce the 4-styryl imidazole (III).Alkylation of imidazole (III) with benzyl chloride leads to a 3:1 mixture of regioisomeric N-benzyl imidazoles (IV) and (V).Ozonolysis of this mixture,followed by oxidative work-up of the ozonide with performic acid,allows isolation of the desired imidazolecarboxylic acid (VI) by employing a differential precipitation technique.Activation of acid (VI) with CDI,and further treatment of the resultant imidazolide with potassium methanenitronate gives rise to nitro ketone (VII).Both nitro groups of (VII) are then reduced by SnCl2 in concentrated HCl to furnish diamine (VIII).Then,removal of the N-benzyl group of (VIII) by catalytic hydrogenation over Pd/C yields imidazole (IX).Ring closure of (IX) in the presence of triethyl orthoformate produces the imidazodiazepinone (X)
合成路线:After silylation of the imidazodiazepinone (X) employing bis(trimethylsilyl)trifluoroacetamide,glycosylation with 2-deoxy-3,5-di-p-toluoyl-D-erythro-pentofuranosyl chloride (XI) leads to a mixture of glycoside anomers (XII) and (XIII),from which the desired beta-anomer (XII) can be isolated by either column chromatography or by fractional crystallization.The toluoyl ester groups of (XII) are then removed by methanolysis in the presence of NaOMe to afford (XIV).Finally,reduction of ketone (XIV) gives rise to a 60:40 mixture of the target (R)-hydroxy imidazodiazepine along with its (S)-epimer (XV),which are separated by reverse-phase preparative HPLC
参考文献标题:Total synthesis of (8R)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol (pentostatin),the potent inhibitor of adenosine deaminase
文献作者:Chan,E.; et al.
参考来源:J Org Chem 1982,47(18),3457
产品链接: CAS No. 53910-25-1›› 产品链接: CAS No.63677-95-2››