AV-100
1-[1(S),2(R)-二(羟甲基)环丙基甲基]-5-[2(E)-溴乙烯基]尿苷Chemical Name: 1-[1(S),2(R)-Bis(hydroxymethyl)cyclopropylmethyl]-5-[2(E)-bromovinyl]uracil
CAS No. 164013-29-0
项目整合开发状态: Preclinical
项目研究机构: Ajinomoto (Originator)
合成路线:The reaction of diethyl malonate (I) with (R)-(-)-epichlorohydrin (II) by means of sodium ethoxide in refluxing ethanol gives the 3-oxa-2-oxobicyclic compound (III),which by reduction with NaBH4 in ethanol yields (1S,2R)-1,2-bis(hydroxymethyl)cyclopropanecarboxylic acid ethyl ester (IV).The reaction of (IV) with diphenyldiazomethane by means of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in dichloroethane affords (1R,7R)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octane-1-carboxylic acid ethyl ester (V),which is reduced with LiBH4 in THF giving the carbinol (VI).The reaction of (VI) with CBr4 and triphenylphosphine in dichloromethane yields the bromomethyl derivative (VII),which is condensed with 5-(2-(E)-bromovinyluracil (VIII) by means of K2CO3 and 18-crown-6 in hot DMF affording the expected addition compound (IX).Finally,this compound is deprotected with HCl in methanol.
📌 参考资料/链接：
参考文献标题:Bis(hydroxymethyl)cyclopropylmethyl pyrimidine derivs.,their preparation and their use as anti-viral agents
文献作者:Onishi,T.; Mukai,C.; Sekiyama,T.; Tsuji,T.; Iwayama,S.; Okunishi,M.(Ajinomoto Co.,Inc.)
参考来源:EP 0649840; JP 1995165731; US 5496824
📄 详细内容
合成路线:The reaction of diethyl malonate (I) with (R)-(-)-epichlorohydrin (II) by means of sodium ethoxide in refluxing ethanol gives the 3-oxa-2-oxobicyclic compound (III),which by reduction with NaBH4 in ethanol yields (1S,2R)-1,2-bis(hydroxymethyl)cyclopropanecarboxylic acid ethyl ester (IV).The reaction of (IV) with diphenyldiazomethane by means of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in dichloroethane affords (1R,7R)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octane-1-carboxylic acid ethyl ester (V),which is reduced with LiBH4 in THF giving the carbinol (VI).The reaction of (VI) with CBr4 and triphenylphosphine in dichloromethane yields the bromomethyl derivative (VII),which is condensed with 5-(2-(E)-bromovinyluracil (VIII) by means of K2CO3 and 18-crown-6 in hot DMF affording the expected addition compound (IX).Finally,this compound is deprotected with HCl in methanol.
参考文献标题:Synthesis and antiviral activity of novel anti-VZV 5-substituted uracil nucleosides with a cyclopropane sugar moiety
文献作者:Onishi,T.; Mukai,C.; Nakagawa,R.; Sekiyama,T.; Aoki,M.; Suzuki,K.; Nakazawa,H.; Ono,N.; Ohmura,Y.; Iwayama,S.; Okunishi,M.; Tsuji,T.
参考来源:J Med Chem 2000,43(2),278
产品链接: CAS No. 164013-29-0››