HAK-2701
Chemical Name: 5'(R)-Ethynyladenosine; 9-(6,7-Dideoxy-beta-D-allo-hept-5-ynofuranosyl)adenine
项目整合开发状态: Biological Testing
项目研究机构: Hokkaido University (Originator), Tokyo Metropolitan Institute of Medical (Originator)
合成路线:The Grignard condensation of the protected adenosine derivative (I) with trimethylsilylethynyl magnesium bromide (II) in THF gives the diastereomeric mixture (III),which is separated by column chromatography.The desired isomer (IV) is treated with ammonia in methanol to yield the isopropylidene derivative of the target compound (V),which is finally deprotected with 90% aqueous TFA.
📌 参考资料/链接：
参考文献标题:Nucleosides and nucleotides.177.9-(6,7-dideoxy-beta-D-allo-hept-5-ynofuranosyl)adenine: A selective and potent ligand for P3 purinoceptor-like protein
文献作者:Matsuda,A.; Kosaki,H.; Saitoh,Y.; Yoshimura,Y.; Minakawa,N.; Nakata,H.
参考来源:J Med Chem 1998,41(15),2676
📄 详细内容
合成路线:The reaction of the protected carbohydrate (I) with trimethylsilylacetylene (II) gives adduct (III) with no stereoselectivity at the reaction point.The oxidation of the OH group of (III) with DMP gives the corresponding oxo compound (IV),which is stereoselectively reduced with N-Selectride to yield the (R)-diastereomer (V) in a 33:1 ratio.The desilylation of (V) with TBAF in THF affords the free compound (VI),which is benzoylated with Bz2O,TEA and DMAP in acetonitrile to provide the tribenzoate (VII).The reaction of (VII) with Ac2O,H2SO4 and AcOH gives the 1-acetoxy compound (VIII),which is condensed with N6-benzoyladenine (IX) by means of Tms-OTf and TEA in acetonitrile,yielding the adenosine derivative (X).Finally,this compound is debenzoylated with ammonia in methanol.
参考文献标题:Nucleosides and nucleotides.Part 201: Alternative method to synthesize 9-(6,7-dideoxy-beta-D-allo-hept-5-ynofuranosyl)adenine,a selective and potent ligand for P-3 purinoceptor-like protein: A stereoselective reduction based on sugar puckering of the fu
文献作者:Umino,T.; et al.
参考来源:Tetrahedron Lett 2000,41(33),6419