-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	476222
标题:	Synthesis of novel nucleotide analogues possessing difluoromethylene phosphonate pharmacophore. Evaluation of the inhibitory activities of PNPases
作者:	Shimeno, H.; Suemune, K.; Abe, H.; Yokomatsu, T.; Kihara, T.; Sato, M.; Soeda, S.; Shibuya, S.
来源:	Symp Med Chem 1998,Abst 1-P-06

合成路线图解说明: 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No.	486236
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
作者:	Yokomatsu, T.; Abe, H.; Sato, M.; Suemune, K.; Kihara, T.; Soeda, S.; Shimeno, H.; Shibuya, S.
来源:	Bioorg Med Chem 1998,6(12),2495

合成路线图解说明: 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.