新产品编号:1359447
Chemical Name: (?-1,1-Difluoro-1-[(1R*,2S*)-2-[2-(6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl]cyclopropyl]methylphosphonic acid; (?-1,1-Difluoro-1-[(1R*,2S*)-2-[2-(hypoxanthin-9-yl)ethyl]cyclopropyl]methylphosphonic acid
项目整合开发状态: Biological Testing
项目研究机构: University of Tokyo (Originator)
合成路线:Treatment of alkenyl iodide (I) with the organozinc reagent (II) in the presence of CuBr afforded the unsaturated alpha,alpha-difluorophosphonate (III),which was condensed with diazomethane to give the cyclopropane derivative (IV).Acid hydrolysis of the tetrahydropyranyl ether of (IV) provided alcohol (V),which was converted into tosylate (VI) with p-TsCl and Et3N.Coupling of (VI) with 6-chloropurine (VII) gave the 9-alkylated purine (VIII).Finally,hydrolysis of both phosphonate esters and the chloro atom of purine (VIII) was carried out upon treatment with bromotrimethylsilane,followed by aqueous hydrolysis to yield the title compound.
📌 参考资料/链接：
参考文献标题:Synthesis of novel nucleotide analogues possessing difluoromethylene phosphonate pharmacophore.Evaluation of the inhibitory activities of PNPases
文献作者:Shimeno,H.; Suemune,K.; Abe,H.; Yokomatsu,T.; Kihara,T.; Sato,M.; Soeda,S.; Shibuya,S.
参考来源:Symp Med Chem 1998,Abst 1-P-06
📄 详细内容
合成路线:Treatment of alkenyl iodide (I) with the organozinc reagent (II) in the presence of CuBr afforded the unsaturated alpha,alpha-difluorophosphonate (III),which was condensed with diazomethane to give the cyclopropane derivative (IV).Acid hydrolysis of the tetrahydropyranyl ether of (IV) provided alcohol (V),which was converted into tosylate (VI) with p-TsCl and Et3N.Coupling of (VI) with 6-chloropurine (VII) gave the 9-alkylated purine (VIII).Finally,hydrolysis of both phosphonate esters and the chloro atom of purine (VIII) was carried out upon treatment with bromotrimethylsilane,followed by aqueous hydrolysis to yield the title compound.
参考文献标题:Synthesis of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids and the related methano analogues.Remarkable effect of the nucleobases and the cyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase
文献作者:Yokomatsu,T.; Abe,H.; Sato,M.; Suemune,K.; Kihara,T.; Soeda,S.; Shimeno,H.; Shibuya,S.
参考来源:Bioorg Med Chem 1998,6(12),2495