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Current Organocatalysis

Author(s): Anirban Mondal and Kartick C. Bhowmick*

DOI: 10.2174/2213337207999200909115215

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Asymmetric Organocatalyzed Warfarin Synthesis in Aqueous and Nonaqueous Media: A Discussion in the Era of COVID-19 Pandemic

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Abstract

The recent widespread infection of COVID-19 in the entire world has created a pandemic situation with a serious health challenge to mankind. Numerous incidents of cardiovascular diseases were found among COVID-19 patients with a significantly high morbidity rate. Medication with several anticoagulant or blood thinner drugs are being performed on COVID-19 patients with atrial fibrillation and cardiovascular ailments to minimize the incidence of death. Warfarin is a widely used anticoagulant and cardiovascular drug prescribed as its sodium salt. S-Enantiomer is two to five times more active than R-enantiomer as an anticoagulant. Synthesis of enantiomerically pure warfarin is thus a rational and extremely important task. Organocatalyzed synthetic strategies may be considered as important avenues to produce optically pure warfarin in comparison to biocatalysis and chiral metal complex catalysis. Herein, a comprehensive review of the asymmetric organocatalyzed synthesis of warfarin catalyzed by diamine based organocatalysts, amino acidbased organocatalysts, quinine based organocatalysts, and proline derived organocatalysts in both aqueous and non-aqueous media has been discussed.

Keywords: COVID-19, cardiovascular diseases, anticoagulant, organocatalysis, warfarin synthesis, michael reaction, aqueous media, non-aqueous media.

Graphical Abstract

[1]
(a) Vetta, F.; Vetta, G.; Marinaccio, L. Coronavirus disease 2019 (COVID-19) and cardiovascular disease: a vicious circle. J. Cardiol. Cardiovasc. Res., 2020, 1-12.
(b) Driggin, E.; Madhavan, M.V.; Bikdeli, B.; Chuich, T.; Laracy, J.; Biondi-Zoccai, G.; Brown, T.S.; Der Nigoghossian, C.; Zidar, D.A.; Haythe, J.; Brodie, D.; Beckman, J.A.; Kirtane, A.J.; Stone, G.W.; Krumholz, H.M.; Parikh, S.A. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J. Am. Coll. Cardiol., 2020, 75(18), 2352-2371.
(c) Fogerty, H.; Townsend, L.; Cheallaigh, C.N.; Bergin, C.; Martin-Loeches, I.; Browne, P.; Bacon, C.L.; Gaule, R.; Gillett, A.; Byrne, M.; Ryan, K.; O’Connell, N.; O’Sullivan, J.M.; Conlan, N.; O’Donnell, J.S. COVID-19 coagulopathy in Caucasian patients. Br. J. Haematol., 2020.
(d) Zhou, F.; Yu, T.; Du, R.; Fan, G.; Liu, Y.; Liu, Z.; Xiang, J.; Wang, Y.; Song, B.; Gu, X.; Guan, L.; Wei, Y.; Li, H.; Wu, X.; Xu, J.; Tu, S.; Zhang, Y.; Chen, H.; Cao, B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020, 395(10229), 1054-1062.
(e) Tang, N.; Li, D.; Wang, X.; Sun, Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost., 2020, 18(4), 844-847.
[http://dx.doi.org/10.1016/j.jacc.2020.03.031] [PMID: 32201335] [http://dx.doi.org/10.1111/bjh.16749] [http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076] [http://dx.doi.org/10.1111/jth.14768] [PMID: 32073213]
[2]
(a) Paranjpe, I.; Fuster, V.; Lala, A.; Russak, A.J.; Glicksberg, B.S.; Levin, M.A.; Charney, A.W.; Narula, J.; Fayad, Z.A.; Bagiella, E.; Zhao, S.; Nadkarni, G.N. Association of treatment dose anticoagulation with In-hospital survival among hospitalized patients with COVID-19. J. Am. Coll. Cardiol., 2020, 76(1), 122-124.
(b) Atallah, B.; Mallah, S.I.; AlMahmeed, W. Anticoagulation in COVID-19. Eur. Heart J. Cardiovasc. Pharmacother., 2020, 6(4), 260-261.
(c) Kollias, A.; Kyriakoulis, K.G.; Dimakakos, E.; Poulakou, G.; Stergiou, G.S.; Syrigos, K. Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action. Br. J. Haematol., 2020, 189(5), 846-847.
(d) Tang, N.; Bai, H.; Chen, X.; Gong, J.; Li, D.; Sun, Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy J. Thrombo. Haemost, 2020.
[http://dx.doi.org/10.1016/j.jacc.2020.05.001] [PMID: 32387623] [http://dx.doi.org/10.1093/ehjcvp/pvaa036] [PMID: 32352517] [http://dx.doi.org/10.1111/bjh.16727] [PMID: 32304577]
[3]
Porter, W.R. Warfarin: history, tautomerism and activity. J. Comput. Aided Mol. Des., 2010, 24(6-7), 553-573.
[http://dx.doi.org/10.1007/s10822-010-9335-7] [PMID: 20352297]
[4]
Meinertz, T.; Kasper, W.; Kahl, C.; Jähnchen, E. Anticoagulant activity of the enantiomers of acenocoumarol. Br. J. Clin. Pharmacol., 1978, 5(2), 187-188.
[http://dx.doi.org/10.1111/j.1365-2125.1978.tb01622.x] [PMID: 619952]
[5]
O’Reilly, R.A. The stereoselective interaction of warfarin and metronidazole in man. N. Engl. J. Med., 1976, 295(7), 354-357.
[http://dx.doi.org/10.1056/NEJM197608122950702] [PMID: 934223]
[6]
Bardsley, H.J.; Daly, A.K. PCT patent WO 00/43003, 2000.
[7]
Bush, E.; Trager, W.F. High-yield synthesis of warfarin and its phenolic metabolites: new compounds. J. Pharm. Sci., 1983, 72(7), 830-831.
[http://dx.doi.org/10.1002/jps.2600720732] [PMID: 6886996]
[8]
Xie, B-H.; Guan, Z.; He, Y-H. Promiscuous enzyme-catalyzed Michael addition: synthesis of warfarin and derivatives. J. Chem. Technol. Biotechnol., 2012, 87, 1709-1714.
[http://dx.doi.org/10.1002/jctb.3830]
[9]
Sano, K.; Saito, S.; Hirose, Y.; Kohari, Y.; Nakano, H.; Seki, C.; Tokiwa, M.; Takeshita, M.; Uwai, K. Development of a novel method for Warfarin synthesis via lipase-catalyzed stereoselective Michael reaction. Heterocycles, 2013, 87, 1269-1278.
[http://dx.doi.org/10.3987/COM-13-12714]
[10]
Robinson, A. Li. H-Y. The first practical asymmetric synthesis of R and S –warfarin. Tetrahedron Lett., 1996, 37, 8321-8324.
[http://dx.doi.org/10.1016/0040-4039(96)01796-0]
[11]
Tsuchiya, Y.; Hamashima, Y.; Sodeoka, M. A new entry to Pd-H chemistry: catalytic asymmetric conjugate reduction of enones with EtOH and a highly enantioselective synthesis of warfarin. Org. Lett., 2006, 8(21), 4851-4854.
[http://dx.doi.org/10.1021/ol0619157] [PMID: 17020319]
[12]
Yang, H-M.; Gao, Y-H.; Li, L.; Jiang, Z-Y.; Lai, G-Q.; Xia, C-G.; Xu, L-W. Iron-catalyzed Michael reactions revisited: a synthetically useful process for the preparation of tri-carbonyl compounds and chiral warfarin. Tetrahedron Lett., 2010, 51, 3836-3839.
[http://dx.doi.org/10.1016/j.tetlet.2010.05.074]
[13]
Leven, M.; Neudörfl, J.M.; Goldfuss, B. Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions. Beilstein J. Org. Chem., 2013, 9, 155-165.
[http://dx.doi.org/10.3762/bjoc.9.18] [PMID: 23400419]
[14]
Rueping, M.; Nachtsheim, B.J.; Sugiono, E. Direct catalytic benzylation of hydroxycoumarin-efficient synthesis of warfarin derivatives and analogues. Synlett, 2010, 1549-1553.
[http://dx.doi.org/10.1055/s-0029-1219936]
[15]
(a) Bhowmick, S.; Mondal, A.; Ghosh, A.; Bhowmick, K.C. Water: The Most Versatile and Nature′s Friendly Media in Asymmetric Organocatalyzed Direct Aldol reactions. Tetrahedron Asymmetry, 2015, 26, 1215-1244.
(b) Ghosh, A.; Bhowmick, S.; Mondal, A.; Garai, H.; Bhowmick, K.C. Advances on Asymmetric Organocatalyzed Mannich Reactions in Aqueous and Non-Aqueous Media. Curr. Organocatal., 2016, 3, 133-160.
(c) Mondal, A.; Bhowmick, S.; Ghosh, A.; Chanda, T.; Bhowmick, K.C. Advances on asymmetric organocatalytic 1, 4-conjugate addition reactions in aqueous and semi-aqueous media. Tetrahedron Asymmetry, 2017, 28, 849-875.
(d) Bhowmick, S.; Kunte, S.S.; Bhowmick, K.C. The Smallest Organocatalyst in Highly Enantioselective Direct Aldol Reaction in Wet Solvent-Free Conditions. RSC Advances, 2014, 4, 24311-24315.
(e) Bhowmick, S.; Kunte, S.S.; Bhowmick, K.C. A New Organocatalyst Derived from Abietic Acid and 4-Hydroxy-L-proline for Direct Asymmetric Aldol Reactions in Aqueous Media. Tetrahedron Asymmetry, 2014, 25, 1292-1297.
(f) Bhowmick, S.; Bhowmick, K.C. Catalytic asymmetric carbon–carbon bond-forming reactions in aqueous media. Tetrahedron Asymmetry, 2011, 22, 1945-1979.
(g) Bhowmick, K.C.; Bihani, M.; Zhao, J.C.G. Organocatalyzed Asymmetric Diels-Alder Reactions in Aqueous or Semi-Aqueous Media. Mini Rev. Org. Chem., 2018, 15, 3-19.
(h) Mondal, A.; Bhowmick, K.C. The carbamate esters as organocatalysts in asymmetric Michael addition reactions in aqueous media: when pyrrolidine backbone surpasses 1,2diaminocyclohexane. ARKIVOC, 2018, 320-331.
(i) Mondal, A.; Bhowmick, K.C. Asymmetric Direct Aldol Reaction Catalyzed by (1R, 2R)-(+)-1,2-Diammonium Cyclohexane-L-tartrate in Water. Curr. Organocatal., 2019, 6, 165-170.
(j) Berkessel, A.; Gröger, H. Asymmetric Organocatalysis From Biomimetic Concepts to Applications in Asymmetric Synthesis. Eds. Wiley-VCH, 2005. ISBN: 978-3-527-30517-9.
(k) Bhowmick, K.C.; Chanda, T. Chapter 12: Asymmetric Organocatalysis in Aqueous MediaGreen Techniques for Organic Synthesis and Medicinal Chemistry (2nd Ed.); Zhang, W.; Cue, B. W. Eds. John Wiley & Sons Ltd.: New Jersey, USA, 2018, pp. 291-324.
[http://dx.doi.org/10.1016/j.tetasy.2015.09.009] [http://dx.doi.org/10.2174/2213337202666150604232523] [http://dx.doi.org/10.1016/j.tetasy.2017.05.011] [http://dx.doi.org/10.1039/C4RA02690J] [http://dx.doi.org/10.1016/j.tetasy.2014.07.012] [http://dx.doi.org/10.1016/j.tetasy.2011.11.009] [http://dx.doi.org/10.2174/1570193X14666170518121235] [http://dx.doi.org/10.24820/ark.5550190.p010.692] [http://dx.doi.org/10.2174/2213337206666181227151140]
[16]
Halland, N.; Hansen, T.; Jørgensen, K.A. Organocatalytic asymmetric Michael reaction of cyclic 1,3-dicarbonyl compounds and α,β-unsaturated ketones--a highly atom-economic catalytic one-step formation of optically active warfarin anticoagulant. Angew. Chem. Int. Ed. Engl., 2003, 42(40), 4955-4957.
[http://dx.doi.org/10.1002/anie.200352136] [PMID: 14579449]
[17]
Kim, H.; Yen, C.; Preston, P.; Chin, J. Substrate-directed stereoselectivity in vicinal diamine-catalyzed synthesis of warfarin. Org. Lett., 2006, 8(23), 5239-5242.
[http://dx.doi.org/10.1021/ol062000v] [PMID: 17078687]
[18]
Mei, R-Q.; Xu, X-Y.; Li, Y-C.; Fu, J-Y.; Huang, Q-C.; Wang, L-X. Highly Effective and Enantioselective Michael Addition of 4-Hydroxycoumarin to α, β-Unsaturated Ketones Promoted by Simple Chiral Primary Amine Thiourea Bifunctional Catalysts. Tetrahedron Lett., 2011, 52, 1566-1568.
[http://dx.doi.org/10.1016/j.tetlet.2011.01.054]
[19]
Rogozi’nska, M.; Adamkiewicz, A.; Mlynarski, J. Efficient “on water” organocatalytic protocol for the synthesis of optically pure warfarin anticoagulant. Green Chem., 2011, 13, 1155-1157.
[http://dx.doi.org/10.1039/c1gc15118e]
[20]
Lim, Y.J.; Kim, D.Y. Enantioselective conjugate addition of 4-hydroxycoumarin to enones catalyzed by binaphthyl-modified primary amine organocatalyst. Bull. Korean Chem. Soc., 2012, 33, 1825-1826.
[http://dx.doi.org/10.5012/bkcs.2012.33.6.1825]
[21]
Dong, J.; Du, D-M. Highly enantioselective synthesis of warfarin and its analogs catalysed by primary amine-phosphinamide bifunctional catalysts. Org. Biomol. Chem., 2012, 10(40), 8125-8131.
[http://dx.doi.org/10.1039/c2ob26334c] [PMID: 22956019]
[22]
Kucherenko, A.S.; Siyutkin, D.E.; Nigmatov, A.G.; Chizhov, A.O.; Zlotin, S.G. Chiral primary amine tagged to ionic group as reusable organocatalyst for asymmetric michael reactions of C-nucleophiles with α,β-unsaturated ketones. Adv. Synth. Catal., 2012, 354, 3078-3086.
[http://dx.doi.org/10.1002/adsc.201200338]
[23]
Rogozinska-Szymczak, M.; Mlynarski, J. Asymmetric synthesis of warfarin and its analogues on water. Tetrahedron Asymmetry, 2014, 25, 813-820.
[http://dx.doi.org/10.1016/j.tetasy.2014.04.008]
[24]
Kucherenko, A.S.; Lisnyak, V.G.; Chizhov, A.O.; Zlotin, S.G. Primary amine attached to an N-(carboxyalkyl)imidazolium cation: a recyclable organocatalyst for the asymmetric Michael reaction. Eur. J. Org. Chem., 2014, 2014, 3808-3813.
[http://dx.doi.org/10.1002/ejoc.201400045]
[25]
Porta, R.; Benaglia, M.; Coccia, F.; Rossi, S.; Puglisi, A. Enantioselective organocatalysis in microreactors: continuous flow synthesis of a (S)-pregabalin precursor and (S)-warfarin. Symmetry (Basel), 2015, 7, 1395-1409.
[http://dx.doi.org/10.3390/sym7031395]
[26]
Kochetkov, S.V.; Kucherenko, A.S.; Zlotin, S.G. Asymmetric synthesis of warfarin and its analogs catalyzed by C2-symmetric squaramide-based primary diamines. Org. Biomol. Chem., 2018, 16(35), 6423-6429.
[http://dx.doi.org/10.1039/C8OB01576G] [PMID: 30047554]
[27]
Kucherenko, A.S.; Kostenko, A.A.; Zhdankina, G.M.; Kuznetsova, O.Y.; Zlotin, S.G. Green asymmetric synthesis of warfarin and coumachlor in pure water catalyzed by quinoline-derived 1,2-diamines. Green Chem., 2018, 20, 754-759.
[http://dx.doi.org/10.1039/C7GC03626D]
[28]
Kristensen, T.E.; Vestli, K.; Hansen, F.K.; Hansen, T. New phenylglycine-derived primary amine organocatalysts for the preparation of optically active warfarin. Eur. J. Org. Chem., 2009, 5185-5191.
[http://dx.doi.org/10.1002/ejoc.200900664]
[29]
Kumagai, J.; Kohari, Y.; Seki, C.; Uwai, K.; Okuyama, Y.; Kwon, E.; Nakano, H. Chiral primary amino amide alcohol organocatalyst for the asymmetric Michael addition of 4-hydroxycoumarin with α,β-unsaturated ketones. Heterocycles, 2015, 90, 1124-1134.
[http://dx.doi.org/10.3987/COM-14-S(K)83]
[30]
Xie, J-W.; Yue, L.; Chen, W.; Du, W.; Zhu, J.; Deng, J-G.; Chen, Y-C. Highly enantioselective michael addition of cyclic 1,3-dicarbonyl compounds to α,β-unsaturated ketones. Org. Lett., 2007, 9(3), 413-415.
[http://dx.doi.org/10.1021/ol062718a] [PMID: 17249775]
[31]
Dong, Z.; Wang, L.; Chen, X.; Liu, X.; Lin, L.; Feng, X. Organocatalytic enantioselective Michael addition of 4-hydroxycoumarin to α, β-unsaturated ketones: a simple synthesis of warfarin. Eur. J. Org. Chem., 2009, 5192-5197.
[http://dx.doi.org/10.1002/ejoc.200900831]
[32]
Isık, M.; Akkoca, H.U.; Akhmedov, I.M.; Tanyeli, C. A bis-Lewis basic 2-aminodmap/prolinamide organocatalysts for application to the enantioselective synthesis of warfarin and derivatives. Tetrahedron Asymmetry, 2016, 27, 384-388.
[http://dx.doi.org/10.1016/j.tetasy.2016.04.001]