[1]严楠,芮培欣,熊斌,等.韦瑞德合成工艺的优化[J].江西师范大学学报(自然科学版),2014,(04):331-335.
 YAN Nan,RUI Pei-xin,XIONG Bin,et al.The Process OPtinization for the Synthesis of Viread[J].,2014,(04):331-335.
点击复制

韦瑞德合成工艺的优化()
分享到:

《江西师范大学学报》(自然科学版)[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2014年04期
页码:
331-335
栏目:
出版日期:
2014-08-31

文章信息/Info

Title:
The Process OPtinization for the Synthesis of Viread
作者:
严楠;芮培欣;熊斌;刘德永;林春花;廖维林
江西师范大学江西省精细化工重点实验室; 国家单糖化学合成工程技术研究中心,江西 南昌 330027;江西师范大学江西省精细化工重点实验室;国家单糖化学合成工程技术研究中心,江西 南昌,330027
Author(s):
YAN Nan;RUI Pei-xin;XIONG Bin;LIU De-yong;LIN Chun-hua;LIAO Wei-lin
关键词:
(R)-9-(2-羟基丙基)腺嘌呤替诺福韦合成韦瑞德
Keywords:
(R)-9-(2-hydroxypropyl)adeninetenofovirsynthesisViread
分类号:
O626;TQ463.53
文献标志码:
A
摘要:
对韦瑞德合成工艺进行优化.以腺嘌呤为起始原料,将其与 R-碳酸丙烯酯缩合反应制得(R)-9-(2-羟基丙基)腺嘌呤,经醚化、超声辅助三甲基氯硅烷脱磷酸酯得到替诺福韦,再经碘甲基碳酸异丙酯酯化、成盐得到最终产物韦瑞德,总收率为31;(以腺嘌呤计算),HPLC 纯度达99.5;.该优化合成工艺成本低廉,收率高,步骤短,适合于工业化生产.
Abstract:
The method for the synthesis of Viread was studied. The target product was synthesized from adenine via ring-opening condensation with(R)-propylene carbonate,etherification and ultrasonic radiation-assisted hydrolysis to give Tenofovir. Which was subjected to reaction with Iodine methyl isopropyl carbonate,followed by salt formation with an overall yield of about 31; ,the HPLC purity was up to 99. 5; . The optimized synthetic process has the ad-vantages of cheapness,high yield,simple and easy work-up. Which was more suitable for industrialized production.

参考文献/References:

d after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus [J].Hepatology,2011,53(3):763-773.
[3] 吴剑涓.抗乙型肝炎病毒药物研究进展 [J].天津药学,2006,18(2):49-52.
[4] Schultze L M,Chapman H H,Dubree N J P,et al.Practical synthesis of the anti-HIV drug,PMPA [J].Tetrahedron Lett,1998,39(14):1853-1856.
[5] Ripin D H B,Teager D,Fortunak J,et al.Process improvements for the manufacture of tenofovir disoproxil fumarate at commercial scale [J].Org Process Res Dev,2010,14(5):1194-1201.
[6] Larrow Jay F,Schaus Scott E,Jacobsen Eric N.Kinetic resolution of terminal epoxides via highly regioselective and enantioselective ring opening with TMSN3.An efficient,catalytic route to 1,2-amino alcohols [J].J Am Chem Soc,1996,118(31):7420-7421.
[7] 夏剑辉,许招会,严楠.甲醇钠催化合成(R)-碳酸丙烯酯 [J].化学世界,2013,54(2):107-109.
[8] Dey S,Garner P.Synthesis of tert-butoxycarbonyl(boc)-protected purines [J].J Org Chem,2000,65(22):7697-7699.
[9] 崔汉峰,袁金斌,王星,等.异丁基硼酸的超声辐射合成 [J].江西师范大学学报:自然科学版,2012,36(4):415-416.
[10] Houghton S R,Melton J,Fortunak J,et al.Rapid,mild method for phosphonate diester hydrolysis:development of a one-pot synthesis of tenofovir disoproxil fumarate from tenofovirdiethyl ester [J].Tetrahedron,2010,66(41):8137-8144.
[11] Bandgar B P,Sarangdhar R J,Ahamed F A,et al.Synthesis,characterization,and biological evaluationof novel diclofenac prodrugs [J].J Med Chem,2011,54(5):1202-1210.

备注/Memo

备注/Memo:
国家科技支撑计划(2009BAI75B02);江西省研究生创新专项基金(YC10A051)
更新日期/Last Update: 1900-01-01