Research progress in the synthesis of L-phenylephrine

doi:10.16085/j.issn.1000-6613.2015.11.035

Abstract

Abstract: L-phenylephrine is an α₁ receptor agonist drug, with vasoconstriction, which is widely used in clinical practice, and its market demand shows a trend of steady growth. Some synthesis methods of L-phenylephrine were reported at home and abroad. However, most of these reports are patents and apart from each other, lack of systematic review. The paper is aimed to summarize various routes for the synthesis of L-phenylephrine and the latest research results, then divides them into two categories, split method and asymmetric synthesis. Both the advantages and disadvantages of each method are reviewed. The traditional split method will continue to play an important role in the production of L-phenylephrine with the racemic synthesis process innovation and the application of new technologies, such as dynamic kinetic resolution. Chemical asymmetric synthesis, after nearly 30 years of research, has been the most economical and effective mean to prepare L-phenylephrine drug, and maintains a good momentum of development. Biological asymmetric synthesis technology will develop gradually from the lab and basic research into application stage. It will occupy a very important position in the synthesis of L-phenylephrine in the future.

Key words: L-phenylephrine, catalyst, selective, synthesis, biocatalysis

摘要： L-去氧肾上腺素是一种α₁受体激动药物,具有血管收缩作用,在临床中应用广泛,并呈稳定的增长趋势。国内外对于合成L-去氧肾上腺素的报道较多,但多为专利且年代跨度大,缺乏系统的综述。本文综述了国内外合成L-去氧肾上腺素的各种工艺路线及最新研究成果,按拆分法和不对称合成法归类,对各合成方法的优缺点进行了评述。传统的拆分法随着消旋体合成工艺的革新、动态动力学拆分等新技术的应用,在L-去氧肾上腺素的生产中将继续发挥作用。化学不对称合成经过近三十年的研究,已成为制备L-去氧肾上腺素药物最经济、有效的合成手段,并保持良好的发展态势。生物不对称合成技术将逐步从实验室和基础研究步入到应用阶段,今后在L-去氧肾上腺素的合成中,将占有十分重要的地位。

关键词: L-去氧肾上腺素, 催化剂, 选择性, 合成, 生物催化

CLC Number:

R972⁺.5

LI Guohua, ZHANG Wenbo, SHI Zhaorui, GENG Peipei, XING Rongfen. Research progress in the synthesis of L-phenylephrine[J]. Chemical Industry and Engineering Progree, 2015, 34(11): 4035-4046.

李国华, 张文博, 石兆瑞, 耿佩佩, 邢荣芬. L-去氧肾上腺素合成研究进展[J]. 化工进展, 2015, 34(11): 4035-4046.

References

[1] Qin Y H,Guillory J K,Schoenwald R D. Formulation,in vitro dissolution,and ocular bioavailability of high- and low-melting phenylephrine oxazolidines[J]. Pharmaceutical Research,1993,10(11):1627-1631.

[2] Dewani A P,Dabhade S M,Bakal R L. Development and validation of a novel RP-HPLC method for simultaneous determination of paracetamol,phenylephrine hydrochloride,caffeine,cetirizine and nimesulide in tablet formulation[J]. Arabian Journal of Chemistry,2013,4(5):501-505.

[3] 王琰,陈文静,周颖,等. 纤维素衍生物手性固定相拆分肾上腺素、盐酸去氧肾上腺素[J]. 药物分析杂志,2012,32(11):1985-1990.

[4] 金有豫. 药理学[M]. 第5版. 北京:人民卫生出版社,2001:39.

[5] Ma J,Wu L N,Hou Z,et al. Visualizing the endocytosis of phenylephrine in living cells by quantum dot-based tracking[J]. Biomaterials,2014,35:7042-7049.

[6] 于彩岩,王海,李晓光,等. 盐酸去氧肾上腺素光学异构体测定方法研究[J]. 内蒙古石油化工,2010(4):9-10.

[7] Dousa M,Gibala P,Havlicek J,et al. Drug-excipient compatibility testing-Identification and characterization of degradation products of phenylephrine in several pharmaceutical formulations against the common cold[J]. Journal of Pharmaceutical and Biomedical Analysis,2011,55:949-956.

[8] 倪永年,桂怿. 微分脉冲伏安法测定药物中盐酸去氧肾上腺素的含量[J]. 南昌大学学报,2009,33(1):35-37.

[9] Legerlotz H. Monohydric amino alcohols and their derivatives:DE,566578[P]. 1927-03-22.

[10] Legerlotz H. Optically active monohydroxyphenylalkylamines:DE,543529[P]. 1929-05-28.

[11] Legerlotz H. Optically active amino alcohols:DE,585164[P]. 1932-06-12.

[12] Legerlotz H. Beta-alkyl-amino compounds of mono-hydroxy-phenyl- ethanols and process of producing same:US,1932347[P]. 1933-10- 24.

[13] 马志聪. 一种去氧肾上腺素的制备方法:中国,101921197[P]. 2010-12-22.

[14] Dousa M,Gibala P,Havlicek J,et al. Drug-excipient compatibility testing-Identification and characterization of degradation products of phenylephrine in several pharmaceutical formulations against the common cold[J]. Journal of Pharmaceutical and Biomedical Analysis,2011,55:949-956.

[15] Bergamann E D,Sulzbacher M. A new synthesis of 1-(m- and p-hydroxyphenyl)-2-methylaminoethanol (m- and p-sympathol)[J]. Journal of Organic Chemistry,1951,16:84-89.

[16] Sun X Y,Rai R,Deschamps J R. Boc-protected 1-(3-oxocycloalkyl) ureas via a one-step Curtius rearrangement:Mechanism and scope[J]. Tetrahedron Letters,2014,55:842-844.

[17] Russel P B,Childress S J. New route to phenylephrine[J]. Journal of Pharmaceutical Sciences,1961,50:713-714.

[18] Hussain A A,Truelove J E,Lawrence,et al. Ester of 3-hydroxy-α- [(methylamino)methyl]benzyl alcohol:US,3825583[P]. 1974-07-23.

[19] Baison W,Teerawutgulrag A,Puangsombat P. An alternative synthesis of (±)-phenylephrine hydrochloride[J]. Maejo International Journal of Science and Technology,2014,8(01):41-47.

[20] Shimojuh N,Imura Y,Moriyama K,et al. Wittig reaction with ion-supported Ph₃P[J]. Tetrahedron,2011,67:951-957.

[21] Bao W N,Pan H F,Zhang Z H,et al. Isolation of the stable strain Labrys sp. BK-8 for L-(+)-tartaric acid production[J]. Journal of Bioscience and Bioengineering,2014,118(1):1-5.

[22] 欧阳敬平,马国振,贾娴. 动态动力学拆分中外消旋化方法的研究进展[J]. 沈阳药科大学学报,2014,31(8):654-657.

[23] 李渤,李晓光,王晓红. L-去氧肾上腺素的制备方法:中国,103772215[P]. 2014-02-19.

[24] 杨少容,胡先明. 手性醇类化合物的构型翻转[J]. 化学试剂,2001,23(1):15-20.

[25] Prasad Divi M K,Krishna L M,Nageswara Rao B,et al. Process for resolution of 1-(3-hydroxyphenyl)-2-methylamino ethanol:US,8455692[P]. 2013-06-04.

[26] Tong S Q,Guan Y X,Yan J Z. Enantiomeric separation of (R,S)-naproxen by recycling high speed counter-current chromatography with hydroxypropyl-β-cyclodextrin as chiral selector[J]. Journal of Chromatography A,2011,1218:5434-5440.

[27] Gurjar M K,Krishna L M,Sarma B V N B S,et al. A practical synthesis of (R)-(-)-phenylephrine hydrochloride[J]. Organic Process Research & Development,1998,2(6):422-424.

[28] Larrow J F. Industrial applications of the jacobsen hydrolytic kinetic resolution technology[J]. Comprehensive Chirality,2012,9:129-146.

[29] Khan N H,Sadhukhan A,Maity N C,et al. Enantioselective O-acetylcyanation/cyanoformylation of aldehydes using catalysts with built-in crown ether-like motif in chiral macrocyclic V(Ⅴ) Salen complexes[J]. Tetrahedron,2011,67:7073-7080.

[30] 程咏梅. 化学酶法催化仲醇的动态动力学拆分[D]. 杭州:浙江大学,2010.

[31] 张怡. 氰醇及不饱和仲醇的动力学拆分研究[D]. 上海:东华大学,2011.

[32] Baumgarten W,Schiffers R. Process for manufacturing of enantiomerically pure 3-hydroxy-3-phenyl-propylamin:US,7294744[P]. 2007-11-13.

[33] Takeda H,Tachinami T,Aburatani M,et al. Practical asymmetric synthesis of (R)-(-)-phenylephrine hydrochloride catalyzed by (2R,4R)-MCCPM-Rhodium complex[J]. Tetrahedron Letters,1989,30(3):367-370.

[34] Sakuraba S,Takahashi H,Takeda T,et al. Efficient asymmetric hydrogenation of α-amino ketone derivatives. A highly enantioselective synthesis of phenylephrine,levamisole,carnitine and propranolol[J]. Chemical and Pharmaceutical Bulletin,1995,43(5):738-747.

[35] Klingler F D,Wolter L,Dietrich W,et al.Verfahren zur herstellung von L-phenylephrin hydrochlorid:DE,19902229[P]. 2002-02-20.

[36] Hossein Michaelson. Synthesis of enantiomerically pure 2-hydroxy- 2-aryl-ethylamines:WO,2009086283[P]. 2008-11-22.

[37] McGarrity J F,Zanotti-Gerosa A. A feasibility study on the synthesis of phenylephrine via ruthenium-catalyzed homogeneous asymmetric hydrogenation[J]. Tetrahedron:Asymmetry,2010(21):2479-2486.

[38] 冯文化,郭方超,于晓丽. L-苯福林盐酸盐的制备方法:中国,102234237[P]. 2011-10-27.

[39] Xing X Y,Zhao Y H,Xu C,et al. Electronic helix theory-guided rational design of kinetic resolutions by means of the Sharpless asymmetric dihydroxylation reactions[J]. Tetrahedron,2012,68:7288-7294.

[40] Devi R,Borah R,Deka C R. Design of zeolite catalysts for Henry reaction under mild condition[J]. Applied Catalysis A:General,2012,433:122-127.

[41] Rajesh K P,Puspesh K U,Pradeep K. Enantioselective synthesis of (R)-phenylephrine hydrochloride[J]. Tetrahedron Letters,2003,44:6245-6246.

[42] Kureshy R I,Dangi B,Das A,et al. Recyclable Cu(Ⅱ)-macrocyclic salen complexes catalyzed Henry reaction of aldehydes:A practical strategy in the preparation of (R)-phenylephrine[J]. Applied Catalysis A:General,2012(439):74-79.

[43] Kureshy R I,Das A,Khan N H,et al. Cu(Ⅱ)-Macrocylic[H₄]salen catalyzed asymmetric Henry reaction and its application in the synthesis of α1-adrenergic receptor agonist (R)-phenylephrine[J]. ACS Catalysis,2011,1(11):1529-1535.

[44] Alvizo O,Collier S J,Hennemann J,et al. Ketoreductase polypeptides for the preparation of phenylephrine:US,20120149073[P]. 2012-06-14.

[45] Lin W D,Chen C Y,Chen H C,et al. Enantioselective synthesis of (S)-phenylephrine by whole cells of recombinant escherichia coli expressing the amino alcohol dehydrogenase gene from rhodococcus erythropolis BCRC 10909[J]. Process Biochemistry,2010,45:1529-1536.

[46] Peng G J,Cho Y C,Fu T K,et al. Enantioselective synthesis of (S)-phenylephrine by recombinant escherichia coli cells expressing the short-chain dehydrogenase/reductase gene from serratia quinivorans BCRC 14811[J]. Process Biochemistry,2013,48:1509-1515.

[47] Peng G J,Kuan Y C,Chou H Y,et al. Stereoselective synthesis of (R)-phenylephrine using recombinant escherichia coli cells expressing a novel short-chain dehydrogenase/reductase gene from serratia marcescens BCRC 10948[J]. Journal of Biotechnology,2014,170:6-9.

[48] LenoX H J,Terentieva E,Gololobov M Y,et al. Optically active fiuorinated vasoconstrictors,methods for making them,and anesthetic formulations comprising them:US,6900203[P]. 2005-05-31.

[49] Tokoshima D,Hanaya K,Shoji M,et al. Whole-cell yeast-mediated preparation of (R)-2-chloro-1-(3-nitrophenyl)ethanol as a synthetic precursor for (R)-phenylephrine[J]. Journal of Molecular Catalysis B:Enzymatic,2013,97:95-99.

[50] Jin Z,Han S Y,Zhang L,et al. Combined utilization of lipase-displaying pichia pastoris whole-cell biocatalysts to improve biodiesel production in co-solvent media[J]. Bioresource Technology,2013,130:102-109.

[51] Navarro R,Ruiz P,Saucedo I,et al. Bismuth(Ⅲ) recovery from hydrochloric acid solutions using Amberlite XAD-7 impregnated with a tetraalkylphosphonium ionic liquid[J]. Separation and Purification Technology,2014,135:268-277.

[52] Jahani F,Tajbakhsh M,Golchoubian H,et al. Guanidine hydrochloride as an organocatalyst for N-Boc protection of amino groups[J]. Tetrahedron Letters,2011,52:1260-1264.

[53] Valizadeh H,Shomali A,Nourshargh S,et al. Carboxyl and nitrite functionalized graphene quantum dots as a highly active reagent and catalyst for rapid diazotization reaction and synthesis of azo-dyes under solvent-free conditions[J]. Dyes and Pigments,2015,113:522-528.

[54] 王波,孙勇,文军. 一种去氧肾上腺素的制备方法:中国,102776251[P]. 2012-08-21.

[55] Breuer M,Pletsch A,Hauer B,et al. Method for producing L-phenylephring using an alcohol dehydrogenase of aromaticum EBN1:US,8617854[P]. 2013-12-31.