目的 研究N⁶-苯甲?；?2'-叔丁基二甲基硅氧基腺苷-3'-H-膦酸的合成工藝。方法 以腺苷為起始原料，先對(duì)腺苷的嘌呤氨基進(jìn)行苯甲?；Ｗo(hù)，再分別向腺苷的5'位和2'位引入二甲氧基三苯甲基（DMT）和叔丁基二甲基硅基（TBDMS）保護(hù)基，制備得到關(guān)鍵中間體N⁶-苯甲酰基-5'-二甲氧基三苯甲氧基-2'-叔丁基二甲基硅氧基腺苷（3）。中間體3與磷試劑2-氯-4H-1，3，2-苯并二氧磷雜環(huán)己烷-4-酮反應(yīng)引入膦酸基團(tuán)，最后使用二氯乙酸脫除DMT保護(hù)基得到目標(biāo)產(chǎn)物。結(jié)果 經(jīng)過(guò)5步反應(yīng)得到了目標(biāo)化合物N⁶-苯甲?；?2'-叔丁基二甲基硅氧基腺苷-3'-H-膦酸，并利用¹H-NMR、³¹P-NMR、質(zhì)譜等方法確證了其結(jié)構(gòu)。本合成工藝的總收率為35.7%，目標(biāo)化合物的質(zhì)量分?jǐn)?shù)為98.5%。結(jié)論 該合成工藝與原有方法相比步驟短，操作簡(jiǎn)單，具有良好的應(yīng)用前景。

Objective To study the synthetic technology of N⁶-benzoyl-2'-O-tert-butyldimethylsilyl-adenosine-3'-yl-H-phosphonate. Methods Adenosine was used as the starting material. The N⁶ amino group of adenosine was protected by benzoyl, following with the introducing protecting groups of dimethoxytrityl (DMT) and tert-butyldimethylsilyl (TBDMS) to the 5' and 2' positions of adenosine respectively, obtaining the key intermediate of N⁶-benzoyl-5'-O-dimethoxytrityl-2'-O-tert-butyldimethylsilyl-adenosine (3). The reagent of 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one was used to introduce phosphonate group to the 3' position of intermediate 3. DMT group was deprotected by dichloroacetic acid and the target compound was obtained. Results The target compound of N⁶-benzoyl-2'-O-tert-butyldimethylsilyl-adenosine-3'-yl-H-phosphonate was achieved and characterized by ¹H-NMR, ³¹P-NMR, and MS. The total yield of this synthetic route was 35.7%. And the purity of target compound was 98.5%. Conclusion The synthetic process is superior to former with simple operations and simplified methods, which has a good application prospect.

國(guó)家自然科學(xué)基金資助項(xiàng)目（31670859）；中國(guó)醫(yī)學(xué)科學(xué)院醫(yī)學(xué)與健康科技創(chuàng)新工程項(xiàng)目（2016-I2M-3-022）；中國(guó)醫(yī)學(xué)科學(xué)院"中央級(jí)公益性科研院所基本科研業(yè)務(wù)費(fèi)"（2016ZX310068、2016ZX310198、2016RC310019、2016RC310017）；協(xié)和小規(guī)模特色辦學(xué)經(jīng)費(fèi)（10023201601602）