Bleomycin A2 sulfate-药物合成数据库

【药物名称】Bleomycin A2 sulfate

化学结构式(Chemical Structure):

参考文献No.	486724
标题:	Five-component synthesis of marimastat analogues
作者:	Patel, S.; et al.
来源:	Tetrahedron Lett 1998,39(45),8333

合成路线图解说明: The reaction of disaccharide (I)(J Org Chem 1981, 46: 3761; ibid. 1985, 50: 5807; ibid. 1986, 51: 189; ibid. 1986, 51: 2927) with HCl in dichloromethane gives the chloride (II), which is condensed with the benzylated histidine derivative (III)(obtained by benzyl esterification of the corresponding free acid (V)(J Am Chem Soc 1979, 101: 3982)) by means of silver triflate yielding the substituted disaccharide (V). The reaction of (V) with tert-butoxycarbonyl anhydride affords compound (VI), which is submitted to hydrogenolysis of this benzyl ester group with H2 over Pd/C giving the acid (VII).

参考文献No.	489172
标题:	Total synthesis of bleomycin group antibiotics. Total syntheses of bleomycin demethyl A2, bleomycin A2, and decarbamoyl bleomycin demethyl A2
作者:	Katano, K.; et al.
来源:	J Am Chem Soc 1998,120(44),11285

合成路线图解说明: The condensation of (VII) with the aminopentanoic benzyl ester (VIII) (obtained by esterification of the corresponding acid (IX) (J Antibiot 1986, 19: 79) with benzyl alcohol/HCl) by means of dicyclohexylcarbodiimide (DCC) and hydroxybenzotriazole (HOBT) yields the amide (X), which is fully debenzylated with H2 over Pd/C in hot ethanol affording the free acid (XI).

合成路线图解说明: The intermediate (XII) has been obtained as follows: The condensation of N-(tert-butoxycarbonyl)-L-threonine (XVIII) with the bithiazole (XIX) (Tetrahedron Lett 1981, 22: 671; J Am Chem Soc 1980, 102: 1452; ibid. 1994, 116: 5607; J Org Chem 1992, 57: 4331) by means of DCC and HOBT as before gives the amide (XX), which is then deprotected with trifluoroacetic acid.

合成路线图解说明: The condensation of (XI) with the bithiazole derivative (XII)(see paragraph 2) by means of DCC and HOBT as before gives intermediate (XIII), which is deprotected with trifluoroacetic acid giving (XIV) with a free amino group.

合成路线图解说明: The condensation of (XIV) with pyrimidinecarboxylic acid (XV)(J Org Chem 1990, 55: 6291) by means of DCC and HOBT as before yields precursor (XVI), which is deacetylated with NH4OH and deprotected with trifluoroacetic acid affording bleomycin demetyl A2 (XVII), which is finally methylated with methyl iodide and copper sulfate in methanol.

合成路线图解说明: The reaction of disaccharide (XXI)(J Org Chem 1981, 46: 3761; ibid. 1985, 50: 5807; ibid. 1986, 51: 189; ibid. 1986, 51: 2927) with HCl in dichloromethane gives the chloride (XXII), which is condensed with the previously described histidine derivative (III) by means of silver triflate yielding the substituted disaccharide (XXIII). The hydrogenolysis of the benzyl ester group of (XXIII) with H2 over Pd/C gives the acid (XXIV), which is condensed with the previously described aminopentanoic benzyl ester (VIII) by means of dicyclohexylcarbodiimide (DCC) and hydroxybenzotriazole (HOBT) yielding the amide (XXV).

合成路线图解说明: The complete debenzylation of (XXV) with H2 over Pd/C in hot ethanol affords the free acid (XXVI), which is condensed with the previously described bithiazole derivative (XII) by means of DCC and HOBT as before giving intermediate (XXVII). The treatment of (XXVII) with trifluoroacetic acid gives (XIV) with a free amino group, and already described in previous schemes.