A Novel Method for the Synthesis of Latanoprost

doi:10.6023/cjoc201403059

Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (9): 1786-1792.DOI: 10.6023/cjoc201403059 Previous Articles Next Articles

一种合成拉坦前列素的新方法

修志明^a, 王立成^b, 黄梦媛^a, 张鹏^a, 郭佑铭^a, 张闻起^a, 王丽萍^a

a 吉林大学生命科学学院, 长春 130012;
b 吉林大学化学学院, 长春 130012

收稿日期:2014-03-27 修回日期:2014-04-23 发布日期:2014-05-23
通讯作者: 王丽萍 E-mail:wanglp@jlu.edu.cn
基金资助:
吉林省自然科学基金(No. 201015171)、吉林省科技发展计划(No. 201205017)、吉林省医药产业发展专项资金(No. YYZX201150-2)、长春市科技局社会发展科技支撑计划(No. 12SF23)资助项目.

A Novel Method for the Synthesis of Latanoprost

Xiu Zhiming^a, Wang Licheng^b, Huang Mengyuan^a, Zhang Peng^a, Guo Youming^a, Zhang Wenqi^a, Wang Liping^a

a School of Life Science, Jilin University, Changchun 130012;
b School of Chemistry, Jilin University, Changchun 130012

Received:2014-03-27 Revised:2014-04-23 Published:2014-05-23
Supported by:
Project supported by the Natural Science Foundation of Jilin Province (No. 201015171), the Scientific and Technological Planning Poject of Jilin Province (No. 201205017), the Pharmaceutical Industry Development Special Fundation Project of Jilin Province (No. YYZX201150-2), and the Social Development Science and Technology Supported Planning Project of Changchun Technology Bureau (No. 12SF23).

Latanoprost is a kind of PGF2α analogues, which is now one of the first-choice drugs in the clinic for open angle glaucoma and ocular hypertension. However, the previous synthetic methods have problems of long steps, low yield and difficult separation of isomeric impurities. Herein, we report a novel method for the synthesis of latanoprost in ten steps. Benzoyl Corey lactone as starting material was oxidized to form corresponding aldehyde by Dess-Martin oxidation. The ω side chain was bonded by improving Horner-Wadsworth-Emmons reaction with dimethyl(2-oxo-4-phenylbutyl)phosphonate and lithium chloride, and reduced with (－)-diisopinocampheyl chloroborane at -30 ℃ because of its greater selectivity towards the production of desired S-isomer (95%). The deprotection step wherein the protecting group of benzoyl on the hydroxyl group of the cyclopentane ring was removed, was preferably carried out by potassium carbonate in methanol. The hydrogenation of double bond in ω side chain was carried out by using 5% palladium-carbon as catalyst. The tetrahydropyranyl (THP) group was used for the protection of the diol with p-toluenesulfonic acid as catalyst. Latanoprost lactol was obtained by reducing the lactone with diisobutylaluminum hydride (DIBAL) at -78 ℃. α side chain of latanoprost was bonded by Wittig reaction with 4-carboxybutyl triphenylphosphoium bromide and NaHMDS forming phosphorus ylide. The carboxylic acid was alkylated with isopropyl iodide in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU), and then removed the THP protecting groups with pyridinium 4-toluenesulfonate (PPTS). Latanoprost was separated from two isomers of 15(S)-latanoprost and 5,6-trans-latanoprost after purification by normal-phase high performance liquid chromatography. Thus latanoprost was obtained with high purity of 99.91% and high overall yield of 19.2%, and the structure was characterized by ¹H NMR, ¹³C NMR, IR and HRMS. Compared with the previous routes, the current synthesis is shorter, more practical, and more suitable for large-scale preparation.

Key words: benzoyl Corey lactone, latanoprost, synthesis, purification

Cite this article

Xiu Zhiming, Wang Licheng, Huang Mengyuan, Zhang Peng, Guo Youming, Zhang Wenqi, Wang Liping. A Novel Method for the Synthesis of Latanoprost[J]. Chin. J. Org. Chem., 2014, 34(9): 1786-1792.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Straus, D.S.; Christopher, K.Med.Res.Rev.2001, 21, 185.
[2] Allaj, V.; Guo, C.; Nie, D.Cell Biosci.2013, 8, 1.
[3] Selliah, R.D.; Hellberg, M.R.; Sharif, N.A.; McLaughlin, M.A.Bioorg.Med.Chem.Lett.2004, 14, 4525.
[4] Han, Z.B.; Chang, Y.P.; Luan, G.Y.; Li, J.; Wang, E.B.Chem.J.Chin.Univ.2002, 23(9), 1660 (in Chinese).(韩正波, 常雅萍, 栾国有, 李娟, 王恩波, 高等学校化学学报, 2002, 23(9), 1660.)
[5] Liu, Z.-Y.; Han, W.-P.Acta Chim.Sinica 1981, 39(4), 424 (in Chinese).(刘志煌, 韩卫平, 化学学报, 1981, 39(4), 424.)
[6] Das, S.; Chandrasekhar, S.; Yadav, J.S.; Gre, R.Chem.Rev.2007, 107, 3286.
[7] Levkoeva, E.I.; Yakhontov, L.N.Russ.Chem.Rev.1977, 46, 565.
[8] Collins, P.W.; Djuric, S.W.Chem.Rev.1999, 93, 1533.
[9] Ying, Y.; Lucitt, M.B.; Stubbe, J.; Yan, C.; Friis, U.G.; Hansen, P.B.; Jensen, B.L.; Smyth, E.M.; FitzGerald, G.A.Proc.Natl.Acad.Sci.U.S.A.2009, 106, 7985.
[10] Perrino, E.; Uliva, C.; Lanzi, C.; Soldato, P.D.; Masini, E.; Sparatore, A.Bioorg.Med.Chem.Lett.2009, 19, 1639.
[11] DeLong, M.A.; Amburgey, J.; Taylor, C.; Wos, J.A.; Soper, D.L.; Wang, Y.L.; Hicks, R.Bioorg.Med.Chem.Lett.2000, 10, 1519.
[12] Feng, Z.X.; Hellberg, M.R.; Sharif, N.A.; McLaughlin, M.A.Bioorg.Med.Chem.2009, 17, 576.
[13] Allaire, C.; Dietrich, A.; Allmeier, H.; Grundmane, I.; Mazur, P.G.; Neshev, P.; Kahle, G.Eur.J.Ophthalmol.2012, 22, 19.
[14] Steigerwalt, R.D.; Vingolo, E.M.; Plateroti, P.; Nebbioso, M.Eur.Rev.Med.Pharmacol.Sci.2012, 16, 1723.
[15] Pacella, F.; Turchetti, P.; Santamaria, V.; Impallara, D.; Smaldone, G.; Brillante, C.; Librando, A.; Damiano, A.; Pecori, G.J.; Pacella, E.Clin.Ophthalmol.2012, 6, 811.
[16] Obadalova, I.; Pilarcik, T.; Slavikova, M.; Hajicek, J.Chirality 2005, 17, 109.
[17] Sharif, N.A.Prostaglandins, Leukotrienes Essent.Fatty Acids 2008, 78, 199.
[18] Klimko, P.; Hellberg, M.; McLaughlin, M.; Sharif, N.Bioorg.Med.Chem.2004, 12, 3451.
[19] Liljebris, C.; Selen, G.; Resul, B.; Stjernschantz, J.; Hacksell, U.J.Med.Chem.1996, 38, 289.
[20] Liu, Z.-Y.; Wu, X.-R.Chin.J.Org.Chem.1981, 1, 104 (in Chinese).(刘志煌, 吴向荣, 有机化学, 1981, 1, 104.)
[21] Martynow, J.G.; wik, J.J.; Szelejewski, W.; Achmatowicz, O.; Kutner, A.; Wisniewski, K.; Winiarski, J.; Zegrocka, S.O.; biewski, P.G.Eur.J.Org.Chem.2007, 689.
[22] Resul, B.; Stjernschantz, J.; No, K.; Liljebris, C.; SelBn, G.; Astin, M.; Karlsson, M.; Bib, L.Z.J.Med.Chem.1993, 36, 243.

一种合成拉坦前列素的新方法

A Novel Method for the Synthesis of Latanoprost

PDF

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Fakai Zou, Nengzhong Wang, Hui Yao, Hui Wang, Mingguo Liu, Nianyu Huang. Regio- and Stereo-selective Synthesis of 1β-/3R-Aryl Thiosugar [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 593-604.
[2]	Luyao Li, Zhongwen He, Zhenguo Zhang, Zhenhua Jia, Teck-Peng Loh. Application of Triaryl Carbenium in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 421-437.
[3]	Qinggang Mei, Qinghan Li. Recent Progress of Visible Light-Induced the Synthesis of C(3) (Hetero)arylthio Indole Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 398-408.
[4]	Penghui Li, Qingyang Xie, Fuxian Wan, Yuanhong Zhang, Lin Jiang. Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 650-656.
[5]	Weiqing Yang, Yanbing Ge, Yuanyuan Chen, Ping Liu, Haiyan Fu, Menglin Ma. Design and Synthesis of Fluorescent 1,8-Napthalimide Derivatives and Their Identification of Cysteine [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 180-194.
[6]	Shihang Yu, Jiawei Liu, Biyu An, Qinghua Bian, Min Wang, Jiangchun Zhong. Asymmetric Synthesis of the Contact Sex Pheromone of Neoclytus acuminatus acuminatus (Fabricius) [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 301-308.
[7]	Qianfan Zhao, Yongzheng Chen, Shiming Zhang. Application and Mechanism Study of Carbon-Based Metal-Free Catalysts in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 137-147.
[8]	Shan Chen, Zhilin Chen, Qiong Hu, Yanshuang Meng, Yue Huang, Pingfang Tao, Liru Lu, Guobao Huang. Recognition of Bis-thiourea Tweezers to Neutral Molecules in Non-Polar Solvent [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 277-281.
[9]	Huakun Wang, Xiaolong Ren, Yining Xuan. Study of the Halide Salt Catalyzed [3＋2] Cycloaddition of α,β-Epoxy Carboxylate with Isocyanate [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 251-258.
[10]	Yukun Jin, Baoyi Ren, Fushun Liang. Visible Light-Mediated Selective C—F Bond Cleavage of Trifluoromethyl Groups and Its Application in Synthesizing gem-Difluoro-Containing Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 85-110.
[11]	Cuiyun Ma, Hailan Luo, Fuhua Zhang, Dan Guo, Shuxing Chen, Fei Wang. Green Biosynthesis, Photophysical Properties and Application of 3-Pyrrolyl BODIPY [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 216-223.
[12]	Bozhen Wang, Jie Zhang, Chunhui Nian, Mingming Jin, Miaomiao Kong, Wulan Li, Wenfei He, Jianzhang Wu. Synthesis and Antitumor Activity of 3,4-Dichlorophenyl Amides [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 232-241.
[13]	Yang Li, Jinding Yuan, Di Zhao. Deep Eutectic Solvent of 1,3-Dimethylurea/L-(+)-Tartaric Acid for the Green Synthesis of (E)-2-Styrylquinoline-3-carboxylic Acid Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3268-3276.
[14]	Dandan Sui, Nannan Cen, Ruoqu Gong, Yang Chen, Wenbo Chen. Supporting-Electrolyte-Free Electrochemical Synthesis of Trifluoromethylated Oxindoles in Continuous Flow [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3239-3245.
[15]	Ruixia Cao, Yuping Jia. Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3304-3311.