一类核苷类似物关键中间体的合成  

Synthesis of the Key Intermediate for a Series of Nucleoside Analogs

作　　者：褚吉成[1] 金汝城[1] 

机构地区：[1]天津大学药物科学与技术学院,天津300072

出　　处：《精细化工》2004年第3期227-229,240,共4页Fine Chemicals

基　　金：国家杰出青年科学基金(30125043);科技部重点基础研究(2002CCA01500)

摘　　要：对一类核苷类似物的关键中间体———(4R,5R) 4 (N 甲基羟氨基) 5 [(叔丁基二苯基硅烷基)氧甲基] 3,4 二氢 2(5H) 呋喃酮的合成进行了研究。以L 抗坏血酸为原料,经Pd/C催化加氢和缩酮保护,生成5,6 O 异亚丙基 L 古洛糖酸 1,4 内酯,产率74 3%。该内酯经NaIO4氧化、Wittig反应、水解成环和柱色谱分离,得(R) (+) 5 羟甲基 2 (5H) 呋喃酮,产率43 0%。最后该呋喃酮再经硅烷保护和羟胺Michael加成,即得到目标化合物。这7步反应的总产率27 9%。Synthesis of (4 R,5R)-4-(N -methyl-hydroxyamino)-5-( tert -butyldiphenylsiloxymethyl)-3,4-dihydro-2(5H)-furanone,key intermediate for a series of nucleoside analogs,was studied.Started from L -ascorbic acid,5,6- O -isopropylidene- L -gulono-1,4-lactone was obtained in 74.3% yield via Pd/C catalytic reduction and ketal protection.The unprotected 2,3-dihydroxyl groups of this lactone were oxidized with NaIO_4 followed by Wittig reaction and deprotection-cyclization reaction to give ( R )-(+)-5-(hydroxymethyl)-2(5H)-furanone in 43.0% yield.The title compound was prepared from this furanone by silica protection and Michael addition.The overall yield of this seven-step reaction was 27.9%.

关 键 词：核苷类似物 MICHAEL加成 L-抗坏血酸 WITTIG反应 

分 类 号：O621.3[理学—有机化学] O622[理学—化学]