光学纯(R)-3-奎宁醇制备技术研究进展
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摘要
抗胆碱能药是一类阻滞乙酰胆碱与胆碱受体相结合的药物,可用于阿尔茨海默病、慢性阻塞性肺病以及尿失禁等多种疾病的治疗.(R)-3-奎宁醇是制备新型抗胆碱能药的关键手性中间体.目前已报道了该手性中间体的多种合成方法,如化学拆分法、化学不对称催化法、酶法拆分以及生物不对称还原法等,其中采用生物不对称还原法制备(R)-3-奎宁醇的产量已达千克级.主要综述了(R)-3-奎宁醇的化学合成法和生物合成法,重点介绍了生物催化不对称还原法制备(R)-3-奎宁醇的研究进展.
Anticholinergics are a kind of drugs that block the combination of acetylcholine with cholinergic receptors,and used for the treatment of a variety of diseases,such as Alzheimers disease,chronic obstructive pulmonary disease and urinary incontinence.(R)-3-quinuclidinol is a key chiral intermediate for numerous new anticholinergics.Up to now,several synthetic methods for this chiral intermediate have been reported,such as chemical resolution,chemical asymmetric catalysis,enzymatic resolution and biological asymmetric reduction.Remarkably,synthesis of(R)-3-quinuclidinol by biological asymmetric reduction has reached kilogram grade.Synthetic routes of(R)-3-quinuclidinol were reviewed in this paper,and the emphasis was focused on biocatalytic asymmetric reduction.
Anticholinergics are a kind of drugs that block the combination of acetylcholine with cholinergic receptors,and used for the treatment of a variety of diseases,such as Alzheimers disease,chronic obstructive pulmonary disease and urinary incontinence.(R)-3-quinuclidinol is a key chiral intermediate for numerous new anticholinergics.Up to now,several synthetic methods for this chiral intermediate have been reported,such as chemical resolution,chemical asymmetric catalysis,enzymatic resolution and biological asymmetric reduction.Remarkably,synthesis of(R)-3-quinuclidinol by biological asymmetric reduction has reached kilogram grade.Synthetic routes of(R)-3-quinuclidinol were reviewed in this paper,and the emphasis was focused on biocatalytic asymmetric reduction.
引文
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[7]胡琦蔚,张俊伟,王远山.生物催化法制备手性酮基布洛芬的研究进展[J].发酵科技通讯,2017,46(3):153-157.
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[24]UZURA A,NOMOTO F,SAKODA A,et al.Stereoselective synthesis of(R)-3-quinuclidinol through asymmetric reduction of 3-quinuclidinone with 3-quinuclidinone reductase of Rhodotorula rubra[J].Applied microbiology&biotechnology,2009,83(4):617-626.
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[26]ISOTANI K,KUROKAWA J,SUZUKI F,et al.Gene cloning and characterization of two NADH-dependent 3-Quinuclidinone reductases from Microbacterium luteolumJCM 9174[J].Applied environment microbiology,2013,79(4):1378-1384.
[27]刘笃强.生物催化不对称合成(R)-3-奎宁醇[D].重庆:重庆医科大学,2016.
[28]ZHANG W X,XU G C,HUANG L,et al.Highly efficient synthesis of(R)-3-Quinuclidinol in a space-time yield of 916g·L-1·d-1 using a new bacterial reductase ArQR[J].Organic letters,2013,15(19):4917-4919.
[29]张文霞.奎宁酮还原酶的挖掘及在制备(R)-3-奎宁醇中的应用性能[D].上海:华东理工大学,2014.
[30]竺伟,高新星,吴会等.重组酮还原酶在制备(R)-3-奎宁酮中的应用:CN 107435042A[P].2017-12-05.
[31]SHINYA I.Method for producing optically active 3-quinuclidinol:JP2002153293[P].2002-05-28.
[32]MAKOTO G,MAKOTO U.Production of R-3-quinuclidinol:JP2000245495[P].2000-09-12.
[33]KAWANO S,NISHIHACHIJYO M,YASOHARA Y,et al.Process for production of(R)-3-quinuclidinol:EP2423320A1[P].2012-02-29.
[34]HOU F,MIYAKAWA T,TAKESHITA D,et al.Expression,purification,crystallization and X-ray analysis of 3-quinuclidinone reductase from Agrobacterium tumefaciens[J].Acta crystallographica,2012,68(10):1237-1239.
[35]SPICKERMANN D,HAUSMANN S,EBER S,et al.Variants of the parvibaculum lavamentivorans short-chain alcohol dehydrogenase:EP2904097[P].2015-06-14.
[36]JIA Z,MA H,HUANG Y,et al.Production of(R)-3-quinuclidinol by a whole-cell biocatalyst with high efficiency[J].Biocatalysis&biotransformation,2017:1-8.
[37]马宏,胡美荣,贾振华,等.一种奎宁酮还原酶KgQR的制备方法及其在制备(R)-3-奎宁醇中应用:CN 106282134A[P].2017-01-04.
[38]罗煜,丁时澄,翟旭东,等.一种羰基还原酶及其在制备(R)-3-奎宁醇中的应用:CN 104830814A[P].2015-08-12.
[39]孙立力,刘笃强,李伟,等.磁性联合交联酶聚集体生物催化剂及其制备方法和应用:CN 107227301A[P].2017-10-03.
[40]何人宝,胡忠梁,金逸中,等.瑞舒伐他汀侧链(3R,5S)-6-R-取代基-3,5-二羟基己酸叔丁酯合成研究进展[J].发酵科技通讯,2017,46(3):188-192.
[41]SPICKERMANN D,HAUSMANN S,DEGERING C,et al.Engineering of highly selective variants of Parvibaculum lavamentivorans alcohol dehydrogenase[J].Chembiochem,2015,15(14):2050-2052.
[2]BEIER J,MROZ R,KIRSTEN A M,et al.Improvement in24-hour bronchodilation and symptom control with aclidinium bromide versus tiotropium and placebo in symptomatic patients with COPD:post hoc analysis of a phase III b study[J].International journal of chronic obstructive pulmonary disease,2017,12:1731-1740.
[3]MAGNUSSEN H,ARZT M,ANDREAS S,et al.Aclidinium bromide improves symptoms and sleep quality in COPD:apilot study[J].European respiratory journal,2017,49(6):1700485.
[4]MCGORUM B C,NICHOLAS D R,FOSTER A P,et al.Bronchodilator activity of the selective muscarinic antagonist revatropate in horses with heaves[J].Veterinary journal,2013,195(1):80-85.
[5]YAMAGUCHI O,KAKIZALI H,HOMMA Y,et al.Solifenacin as add-on therapy for overactive bladder symptoms in men treated for lower urinary tract symptoms-assist,randomized controlled study[J].Urology,2011,78(1):126-133.
[6]KARRAM M,TOGLIA M S,ANDOH M,et al.Treatment with solifenacin increases warning time and improves symptoms of overactive bladder:results from VENUS,a randomized,double-blind,placebo-controlled trial[J].Urology,2009,73(1):14-18.
[7]胡琦蔚,张俊伟,王远山.生物催化法制备手性酮基布洛芬的研究进展[J].发酵科技通讯,2017,46(3):153-157.
[8]BORNSCHEUER U T,HUISMAN G W,KAZLAUSKAS R J,et al.Engineering the third wave of biocatalysis[J].Nature,2012,485:185-194.
[9]李书彬,申永存,曾鹏.3-奎宁醇的拆分研究[J].安徽化工,2009,35(1):31-33.
[10]JI J G,LI T,WANG Y.3-Quinuclidinyl amino-substituted biaryl derivatives:US7309699[P].2007-12-18.
[11]TSUTSUMI K,KATAYAMA T,UTSUMI N,et al.Practical asymmetric hydrogenation of 3-quinuclidinone catalyzed by the XylSkewphos/PICA-Ruthenium(II)complex[J].Organic process research&development,2009,13(3):625-628.
[12]ARAI N,AKASHI M,SUGIZAKI S,et al.Asymmetric hydrogenation of bicyclic ketones catalyzed by BINAP/IPHAN-Ru(II)complex[J].Organic letters,2010,12(15):3380-3383.
[13]徐亮.一种制备(R)-3-奎宁环醇的方法:CN105085513A[P].2015-11-25.
[14]NOMOTO F,HIRAYAMA Y,IKUNAKA M,et al.A practical chemoenzymatic process to access(R)-quinuclidin-3-ol on scale[J].Tetrahedron asymmetry,2003,14(13):1871-1877.
[15]MUCHMORE D C.Enantiomeric enrichment of(R,S)-3-quinuclidinol:US,EP 0577253A2[P].1993-06-01.
[16]PRIMOZIC I,BOLANT M,RAMIC A,et al.Preparation of novel meta-and para-substituted N-benzyl protected quinuclidine esters and their resolution with butyrylcholinesterase[J].Molecules,2012,17(1):786-795.
[17]白东亚,何军邀,欧阳斌,等.手性芳基醇的生物催化不对称合成[J].化学进展,2017,29(5):491-501.
[18]TORRELO G,HANEFELD U,HOLLMANN F.Biocatalysis[J].Catalysis letter,2015,145(1):309-345.
[19]BOMMARIUS A S.Biocatalysis:a status report[J].Annual review of chemical&biomolecular engineering,2015,6(1):319-345.
[20]何军邀,白东亚,王普.恶臭假单胞菌产羰基还原酶的发酵条件优化[J].发酵科技通讯,2017,46(4):243-248.
[21]邱健,张霞,马宏,等.转化奎宁酮为(R)-3-奎宁醇菌株的筛选及转化条件优化[J].微生物学通报,2011,38(5):736-742.
[22]KOLET S P,JADHAV D D,PRIYADARSHINI B,et al.Fungi mediated production and practical purification of(R)-(-)-3-quinuclidinol[J].Tetrahedron letters,2014,55(43):5911-5914.
[23]WANG Y,LI J,WU Q,et al.Microbial stereospecific reduction of 3-quinuclidinone with newly isolated Nocardiasp.and Rhodococcus erythropolis[J].Journal of molecular catalysis B enzymatic,2013,88:14-19.
[24]UZURA A,NOMOTO F,SAKODA A,et al.Stereoselective synthesis of(R)-3-quinuclidinol through asymmetric reduction of 3-quinuclidinone with 3-quinuclidinone reductase of Rhodotorula rubra[J].Applied microbiology&biotechnology,2009,83(4):617-626.
[25]ISOTANI K,KUROKAWA J,ITOH N.Production of(R)-3-quinuclidinol by E.coli biocatalysts possessing NADH-dependent 3-Quinuclidinone reductase(QNR or bacC)from Microbacterium luteolum and Leifsonia alcohol dehydrogenase(LSADH)[J].International journal of molecular sciences,2012,13(10):13542-13553.
[26]ISOTANI K,KUROKAWA J,SUZUKI F,et al.Gene cloning and characterization of two NADH-dependent 3-Quinuclidinone reductases from Microbacterium luteolumJCM 9174[J].Applied environment microbiology,2013,79(4):1378-1384.
[27]刘笃强.生物催化不对称合成(R)-3-奎宁醇[D].重庆:重庆医科大学,2016.
[28]ZHANG W X,XU G C,HUANG L,et al.Highly efficient synthesis of(R)-3-Quinuclidinol in a space-time yield of 916g·L-1·d-1 using a new bacterial reductase ArQR[J].Organic letters,2013,15(19):4917-4919.
[29]张文霞.奎宁酮还原酶的挖掘及在制备(R)-3-奎宁醇中的应用性能[D].上海:华东理工大学,2014.
[30]竺伟,高新星,吴会等.重组酮还原酶在制备(R)-3-奎宁酮中的应用:CN 107435042A[P].2017-12-05.
[31]SHINYA I.Method for producing optically active 3-quinuclidinol:JP2002153293[P].2002-05-28.
[32]MAKOTO G,MAKOTO U.Production of R-3-quinuclidinol:JP2000245495[P].2000-09-12.
[33]KAWANO S,NISHIHACHIJYO M,YASOHARA Y,et al.Process for production of(R)-3-quinuclidinol:EP2423320A1[P].2012-02-29.
[34]HOU F,MIYAKAWA T,TAKESHITA D,et al.Expression,purification,crystallization and X-ray analysis of 3-quinuclidinone reductase from Agrobacterium tumefaciens[J].Acta crystallographica,2012,68(10):1237-1239.
[35]SPICKERMANN D,HAUSMANN S,EBER S,et al.Variants of the parvibaculum lavamentivorans short-chain alcohol dehydrogenase:EP2904097[P].2015-06-14.
[36]JIA Z,MA H,HUANG Y,et al.Production of(R)-3-quinuclidinol by a whole-cell biocatalyst with high efficiency[J].Biocatalysis&biotransformation,2017:1-8.
[37]马宏,胡美荣,贾振华,等.一种奎宁酮还原酶KgQR的制备方法及其在制备(R)-3-奎宁醇中应用:CN 106282134A[P].2017-01-04.
[38]罗煜,丁时澄,翟旭东,等.一种羰基还原酶及其在制备(R)-3-奎宁醇中的应用:CN 104830814A[P].2015-08-12.
[39]孙立力,刘笃强,李伟,等.磁性联合交联酶聚集体生物催化剂及其制备方法和应用:CN 107227301A[P].2017-10-03.
[40]何人宝,胡忠梁,金逸中,等.瑞舒伐他汀侧链(3R,5S)-6-R-取代基-3,5-二羟基己酸叔丁酯合成研究进展[J].发酵科技通讯,2017,46(3):188-192.
[41]SPICKERMANN D,HAUSMANN S,DEGERING C,et al.Engineering of highly selective variants of Parvibaculum lavamentivorans alcohol dehydrogenase[J].Chembiochem,2015,15(14):2050-2052.