SR-3785
Chemical Name: 5(R)-(2-Amino-9H-purin-9-ylmethoxy)-2-hydroxy-1,2-oxaphosphorinan-2-one; 9-[(5R)-2-Hydroxy-2-oxo-1,2-oxaphosphorinan-5-yloxymethyl]-9H-purin-2-amine
CAS No. 198267-75-3
项目整合开发状态: Preclinical
项目研究机构: SRI (Originator)
合成路线:Regiospecific opening of the chiral 2-(benzyloxymethyl)oxirane (I) with lithiated diethyl methylphosphonate in the presence of boron trifluoride etherate afforded phosphonate (III).After conversion of (III) to the chloromethyl ether (IV),upon treatment with paraformaldehyde and HCl,condensation with the sodium salt of 2-amino-6-chloropurine (V) gave the nucleoside phosphonate (VI).Simultaneous hydrogenolysis of the chlorine atom and benzyl ether of (VI) by transfer hydrogenation in the presence of ammonium formate and Pd/C yielded (VII).Finally,the phosphonate ester groups of (VII) were cleaved by means of bromotrimethylsilane.
合成路线:Regiospecific opening of the chiral 2-(benzyloxymethyl)oxirane (I) with lithiated diethyl methylphosphonate in the presence of boron trifluoride etherate afforded phosphonate (III).After conversion of (III) to the chloromethyl ether (IV),upon treatment with paraformaldehyde and HCl,condensation with the sodium salt of 2-amino-6-chloropurine (V) gave the nucleoside phosphonate (VI).Simultaneous hydrogenolysis of the chlorine atom and benzyl ether of (VI) by transfer hydrogenation in the presence of ammonium formate and Pd/C yielded (VII).The phosphonate ester groups of (VII) were then cleaved by means of bromotrimethylsilane to give phosphonic acid (VIII).Finally,intramolecular cyclization of (VIII) by treatment with DCC furnished the title compound.
📌 参考资料/链接：
参考文献标题:Enantiomerically pure 2-aminopurine phosphonate nucleotide analogs as antiviral agents
文献作者:Reist,E.J.; Bradford,W.W.; Zaveri,N.T.(SRI International)
参考来源:US 5877166; WO 9741133
📄 详细内容
合成路线:Regiospecific opening of the chiral 2-(benzyloxymethyl)oxirane (I) with lithiated diethyl methylphosphonate in the presence of boron trifluoride etherate afforded phosphonate (III).After conversion of (III) to the chloromethyl ether (IV),upon treatment with paraformaldehyde and HCl,condensation with the sodium salt of 2-amino-6-chloropurine (V) gave the nucleoside phosphonate (VI).Simultaneous hydrogenolysis of the chlorine atom and benzyl ether of (VI) by transfer hydrogenation in the presence of ammonium formate and Pd/C yielded (VII).Finally,the phosphonate ester groups of (VII) were cleaved by means of bromotrimethylsilane.
合成路线:Regiospecific opening of the chiral 2-(benzyloxymethyl)oxirane (I) with lithiated diethyl methylphosphonate in the presence of boron trifluoride etherate afforded phosphonate (III).After conversion of (III) to the chloromethyl ether (IV),upon treatment with paraformaldehyde and HCl,condensation with the sodium salt of 2-amino-6-chloropurine (V) gave the nucleoside phosphonate (VI).Simultaneous hydrogenolysis of the chlorine atom and benzyl ether of (VI) by transfer hydrogenation in the presence of ammonium formate and Pd/C yielded (VII).The phosphonate ester groups of (VII) were then cleaved by means of bromotrimethylsilane to give phosphonic acid (VIII).Finally,intramolecular cyclization of (VIII) by treatment with DCC furnished the title compound.
参考文献标题:Enantiomerically pure 2-aminopurine cyclic and acyclic nucleotide phosphonate analogs as antiviral agents aganist human cytomegalovirus
文献作者:Zaveri,N.; et al.
参考来源:219th ACS Natl Meet (March 26 2000,San Francisco) 2000,19Abst MEDI 129