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[1]古双喜,段婷,乔恒,等.马来酸罗格列酮合成研究进展[J].武汉工程大学学报,2013,(09):1-6.[doi:103969/jissn16742869201309001]
　GU Shuang\|xi,DUAN Ting,QIAO\|Heng,et al.Advance on synthesis of Rosiglitazone Maleate[J].Journal of Wuhan Institute of Technology,2013,(09):1-6.[doi:103969/jissn16742869201309001]
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马来酸罗格列酮合成研究进展(/HTML)
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
期数:
2013年09期
页码:
1-6
栏目:
化学与化学工程
出版日期:
2013-10-10

文章信息/Info

Title:
Advance on synthesis of Rosiglitazone Maleate
文章编号:
16742869(2013)09000106
作者:
古双喜; 段婷; 乔恒; 陈金芳; 巨修练
武汉工程大学化工与制药学院，湖北省新型反应器与绿色化学工艺重点实验室，湖北 武汉 430074
Author(s):
GU Shuang\|xi;  DUAN Ting;  QIAO\|Heng;  CHEN Jin\|fang;  JU Xiu\|lian
Hubei Key Lab of Novel Reactor & Green Chemical Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430074, China
关键词:
马来酸罗格列酮; 合成路线; 噻唑烷二酮类; 胰岛素增敏剂
Keywords:
rosiglitazone maleate;  synthetic route;  thiazolidinediones;  insulin sensitizer
分类号:
TQ463
DOI:
103969/jissn16742869201309001
文献标志码:
A
摘要:
罗格列酮(RSG)是一种噻唑烷二酮类胰岛素增敏剂，1999年5月马来酸罗格列酮(RSGM)被美国食品与药物管理局批准上市，用于非胰岛素依赖型（NIDDM型/Ⅱ型）糖尿病的治疗.国内外文献中报道的RSG和RSGM的合成方法较多，根据不同的起始原料及合成工艺RSG和RSGM及其关键中间体的合成路线主要有：以2,5\|二溴吡啶为原料经4步反应可制备RSG，RSG与马来酸成盐即得RSGM，该法反应条件温和，但是原料价格较贵，且反应的原子经济性不高；以2\|溴吡啶或2\|氯吡啶为原料的合成工艺有多条，以4\|羟甲基苯酚为原料的合成路线因试剂毒性大、价格高，不适于工业化；以4\|羟基苯甲醛为原料的合成路线有两条，其中一条中的醚化反应要用到N,N’\|二环己基碳二亚胺，成本较高，第二条路线复杂冗长，操作繁琐，亦不理想；以对氟苯甲醛为原料的合成路线因原料价格较贵，缺乏竞争力；其中以2\|氯吡啶为原料、4\|\[2\|(甲基\|2\|吡啶基氨基)\|乙氧基\]\|苯甲醛为关键中间体的合成路线最具吸引力.
Abstract:
Rosiglitazone (RSG) is a thiazolidinedione insulin sensitizer, which was approved by American Food and Drug Administration (FDA) in the form of Rosiglitazone Maleate (RSGM) for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) or diabetes mellitus type II. At present, many synthetic methods of RSG and RSGM were reported. Base on different starting materials and synthetic technology, the synthetic routes of RSG and RSGM as well as their key intermediates were reviewed as follows: The reaction conditions of preparing RSG from 2,5-dibromopyridine via 4-step reactions are mild but with expensive starting materials and low atom economy; most of the synthetic routes of RSGM are from the starting material 2-bromopyridine or 2-chloropyridine, among which the synthetic route of RSGM with 2-chloropyridine as starting material and 4-(2-(methyl(pyridin-2- yl)amino)ethoxy)benzaldehyde as key intermediate is the most attractive one; the synthetic route of RSGM from 4-hydroxymethylphenol is not suitable for industrialization due to the high toxicity and high price of reaction reagents; one of the two synthetic routes from 4-hydroxybenzaldehyde is high-cost due to the use of NN’Dicyclohexylcarbodie in the etherification reaction, and the other route is tedious and non-ideal; the two routes of preparing RSGM from p-fluorobenzaldehyde are less competitive due to the expensive starting material.

参考文献/References:

［1］Cantello B C, Cawthorne M A, Haigh D, et al. The synthesis of BRL 49653\|a novel and potent antihyperglycaemic agent ［J］. Bioorg Med Chem Lett, 1994, 4(10): 1181\|1184.［2］Smith S, 罗格列酮改善胰岛素抵抗和β细胞功能及对心血管的潜在保护作用 ［J］. 国外医学内分泌学分册, 2002, 22(5): 284\|286.Smith S. The improvement of insuline resistance and β cell function of Rosiglitazone and its potential protective effect on angiocarpy ［J］. Foreign Med Sci (Section Endocrin). 2002, 22(5): 284\|286.［3］Lebovitz H E, Dole J F, Patwardhan R, et al. Rosiglitazone monotherapy is effective in patients with type 2 diabetes ［J］. J Clin Endocrinol Metab, 2001, 86(1): 280\|288.［4］Willson T M, Cobb J E, Cowan D J, et al. The structure\|activity relationship between peroxisome proliferator\|activated receptor γ agonism and the antihyperglycemic activity of thiazolidinediones ［J］ . J Med Chem, 1996, 39(3): 665\|668.［5］王恩思, 王俊才, 姜作辉, 等. 马来酸罗格列酮的合成［J］. 吉林大学自然科学学报, 2000, 3(3): 68\|72.Wang E S, Wang J C, Jiang Z H, et al. Synthesis of Rosiglitazone Maleate ［J］. Acta Scientiarum Naturalium Universitatis Jilinensis, 2000, 3(3): 68\|72.（in Chinese）［6］Modi I A, Shukla D, Chandrakant M, et al. An improved process for the preparation of 4\|［2\|(methyl\|2\| pyridinylamino)ethoxy］ benzaldehyde, an intermediate for the preparation of rosiglitazone: EP, 1905761［P］. 2007\|09\|22.［7］雷琴, 广兵, 王良兵, 等. 罗格列酮的合成 ［J］. 四川大学学报, 2003, 35(3), 107\|109.Lei Q, Guang B, Wang L B, et al. Synthesis of Rosiglitazone ［J］. Journal of Sichuan University (Engineering Science edition), 2003, 35(3), 107\|109.（in Chinese）［8］Gaonkar S L, Shimizu H. Microwave\|assisted synthesis of the antihyperglycemic drug rosiglitazone ［J］. Tetrahedron, 2010, 66(18): 3314\|3317.［9］Winiarski J, Plesniak K. Method of obtaining 5\|［4\|［2\|(N\|methyl\|N\|(pyridil\|2\|)\|amino)\|etho\|xy］\|benzyl］\|thiazolydin\|2,4\|dione: PL, 194428［P］. 2003\|05\|05.［10］Shimamura H, Kagara K. Method for producing 2\|imino\|4\|thiazolidinone derivative and 2,4\|thiazolidine\| dione derivative : JP, 2009209106［P］. 2009\|09\|17.［11］Kankan R N, Rao D R. Process for the preparation of rosiglitazone: GB, 2413795 ［P］.2004\|05\|05.［12］Li X, Abell C, Warrington B H, et al. Polymer\|assisted solution phase synthesis of the antihyperglycemic agent Rosiglitazone (Avandia?) ［J］. Org Biomol Chem, 2003, 1(24): 4392\|4395.［13］Halama A, Jirman J. Method for the preparation of rosiglitazone: WO, 2006032218［P］. 2005\|08\|31.［14］Giles R G, Lewis N J, Quick J K, et al. Regiospecific reduction of 5\|benzylidene\|2, 4\|thiazolidinediones and 4\|oxo\|2\|thiazolidinethiones using lithium borohydride in pyridine and tetrahydrofuran ［J］. Tetrahedron, 2000, 56(26): 4531\|4537.［15］Giles R, Lewis N, Moore S, et al. Process for the preparation of substituted thiazolidinedione:WO, 1998037073 ［P］.1998\|02\|13.［16］刘昆,李彦. 一种制备噻唑烷二酮类化合物的方法: CN, 1840526［P］. 2006\|10\|04.Liu K, Li Y. A method for preparing Thiazolidinediones. CN, 1840526［P］. 2006\|10\|04.（in Chinese）［17］王建村,史大勇,谢春红. 噻唑烷二酮类化合物的制备方法: CN, 10875656［P］. 2010\|11\|03.Wang J C, Shi D Y, Xie C H. The preparing method of Thiazolidinediones. CN, 10875656［P］. 2010\|11\|03.（in Chinese）［18］Heath C M, Imrie RC, Jones J J, et al. Whole Cell Biotransformation of 5\|(4\|(2\|(2\|Pyridyl) methylamino) ethoxy) benzylidenethiazolidine\|2, 4\|dione to its Benzyl Derivative Using a Yeast Reductase ［J］. J Chem Technol Biot, 1997, 68(3): 324\|330.［19］Hindley R, Woroniecki S. Process for the prepapation of pharmaceutically active thiazolidine or oxazolidine compounds by a yeast reductase: WO, 1993010254［P］. 1993\|05\|27.［20］Namblar S, Pise A. Process for preparing thiazolidine\|diones: WO, 2005049610［P］. 2005\|06\|02.［21］Venkatasubramanian H, Bandi V R, Kodali H P. Reducion of the exocyclic double bond of substituted thiazolidine diones by hantzsch 1,4\|dihydropyridine ［J］. Indian J Heterocy CH, 2006, 15: 407\|408.［22］Duran López E, Tojo Suárez G, Process for the preparation of rosiglitazone: WO, 2005108394 ［P］. 2005\|11\|17.［23］Duran LE. Process for preparation of intermediates of rosiglitazone, rosiglitazone and new polymorphic forms thereof: WO, 2008010089［P］. 2008\|01\|24.［24］张爱华, 沈义鹏, 丁娅. 罗格列酮的合成 ［J］. 齐鲁药事, 2005, 24(11): 685\|687.Zhang A H, Shen Y P, Ding Y. Chemical synthesis of Rosiglitazone ［J］. Oilu Pharmaceutical Affairs, 2005, 24(11): 685\|687.（in Chinese）［25］Brummond K M, Lu J. Solid\|phase synthesis of BRL 49653 ［J］. J Org Chem, 1999, 64(5): 1723\|1726.［26］Jawale D V, Pratap U R, Mane RA. An alternative synthetic route for an antidiabetic drug, rosiglitazone［J］. Bioorg Med Chem Lett, 2012, 22(2): 924\|928.［27］杨德红. Ⅱ型糖尿病新药罗格列酮的合成工艺研究和相关药物中间体的合成反应研究［D］. 杭州：浙江大学, 2003.Yang D H. Synthetic route of new drug Rosiglitazone against diabetes mellitus type II and synthetic reaction of relevant drug intermediates ［D］.Hangzhou: Zhejiang University, 2003.（in Chinese）［28］Ujire S, Sridharan M, Ganesh S. Novel process for the synthesis of thiazolidione derivatives: WO, 2003029251 ［P］. 2004\|04\|10.

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备注/Memo

备注/Memo:
收稿日期：20130923基金项目：湖北省新型反应器和绿色化学工艺重点实验室开放基金(RGCT201201)；武汉工程大学科学研究基金(10128301)作者简介：古双喜（1979-），男，湖北黄冈人，博士，硕士研究生导师. 研究方向：药物合成工艺，药物化学，有机合成.
更新日期/Last Update: 2013-10-11