Asymmetric Reduction of Heteroaryl Methyl Ketones Using Daucus carota
Ch Sree Lakshmi, Goka Roopa Reddy, Adari Bhaskar Rao
DOI: 10.4236/gsc.2011.14019   PDF    HTML     6,576 Downloads   13,072 Views   Citations


Asymmetric reduction of the heteroaryl prochiral ketones to corresponding chiral alcohols by Daucus carota was studied. The study highlights selective bioreduction of different substituted heteroaryl ketones (1a - 1j) to their respective chiral alcohols (2a - 2j) using plant dehydrogenase enzymes present in Daucus carota in good yields (60% - 95%) and enantioselectivity (76% - 99%) with S-form configuration. The results obtained confirm that the membrane bound dehydrogenase enzyme has broad substrate specificity and selectivity in catalyzing both six and five membered heteroaryl methyl ketones. The present methodology demonstrates promising and alternative green route in the synthesis secondary chiral alcohols of biologically importance in a simple, inexpensive and eco-friendly process.

Share and Cite:

C. Lakshmi, G. Reddy and A. Rao, "Asymmetric Reduction of Heteroaryl Methyl Ketones Using Daucus carota," Green and Sustainable Chemistry, Vol. 1 No. 4, 2011, pp. 117-122. doi: 10.4236/gsc.2011.14019.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] C. W. Bradshaw, W. Hummel and C. H. Wong, “Lacto- bacillus kefir Alcohol Dehydrogenase: A Useful Catalyst for Synthesis,” Journal of Organic Chemistry, Vol. 57, No. 5, 1992, pp. 1532-1536. doi:10.1021/jo00031a037
[2] R. N. Patel, M. -R. Kula and U. Kragl, “Dehydrogenases in the Synthesis of Chiral Compounds in: ‘Stereo-selec- tive Biocatalysis’,” Marcel Decker, New York, 2002, pp. 839-866.
[3] K. Faber, “Biotransformations in Organic Chemistry,” Springer Verlag, Berlin, 2004. doi:10.1007/978-3-642-18537-3
[4] C. A. Challenger, “Chiral Drugs,” John Willey & Sons, New York, 2001.
[5] V. Gotor, I.Alfonso and E.Garcia-Urdiales, “Asymmetric Organic Synthesis with Enzymes,” Wiley, Weinheim, 2008.doi:10.1002/9783527622481
[6] T. Matsuda, R. Yamanaka and K. Nakamura, “Recent Progress in Biocatalysts for Asymmetric Oxidation and Reduction,” Tetrahedron: Asymmetry, Vol. 20, No. 5, 2009, pp. 513-557. doi:10.1016/j.tetasy.2008.12.035
[7] H. Y. Yale, “Pyridine and Its Derivatives: Ppart 2,” In: E. Klingsberg, Ed., Interscience Publisher INC., New York, 1961.
[8] P. Hayoz, A. von Zelewsky and H. Stoeckli-Evans, “Ste- reoselective Synthesis of Octahedral Complexes with Predetermined Helical Chirality,’’ Journal of American Chemical Society, Vol. 115, No. 12, 1993, pp. 5111- 5114. doi:10.1021/ja00065a023
[9] S. Kawano, M. Horikawa, Y. Yasohara and J. Hasega- wa,“Microbial Enantioselective Reduction of Acetyl Pyridine Derivatives,” Bioscience, Biotechnology and Biochemistry, Vol. 67, No. 4, 2003, pp. 809-814. doi:10.1271/bbb.67.809
[10] F. Baldassarre, G. Bertoni, C. Chiappe and F. Marioni, “Preparative Synthesis of Chiral Acohols by Enantiose- lective Reduction with Daucus carota Root a Biocata- lyst,” Journal of Molecular Catalysis B: Enzymes, Vol. 11, No. 1, 2000, pp. 55-58. doi:10.1016/S1381-1177(00)00189-2
[11] A. A. Orden, F, R. Bisogno, D. A. Cifuente, O. S. Gior- dano and M. Kurina Sanz, “Asymmetric Bioreduction of Natural Xenobiotic Diketones by Brassica napus Hairy Roots,” Journal of Molecular Catalysis B: Enzymes, Vol. 42, No. 3-4, 2006, pp. 71-77. doi:10.1016/j.molcatb.2006.06.010
[12] K. Matsuo, Sei-ichiro Kawabe, Y. Tokuda, T. Eguchi, R. Yamanaka and K. Nakamura, “Asymmetric Reduction of Ketones with a Germinated Plant,” Tetrahedron: Asym- metry, Vol. 19, No. 2, 2008, pp. 157-159. doi:10.1016/j.tetasy.2007.12.015
[13] M. Petersen and A. Kiener, “Preparation and Functiona- lization of N-Heterocycles,’’ Green Chemistry, Vol. 1, No. 2, 1999, pp. 99-106. doi:10.1039/a809538h
[14] N. Blanchard and P. van de Weghe, “Daucus carota Me- diated Bioreduction of Prochiral Ketones,’’ Organic Bio- molecular Chemistry, Vol. 4, No. 12, 2006, pp. 2348- 2353. doi:10.1039/b605233a
[15] R. Lacheretz, D. G. Pardo and J. Cossy, “Daucus carota Mediated Reduction of Cyclic 3-Oxo-amines,” Organic Letters, Vol. 11, No. 6, 2009, pp. 1245-1248. doi:10.1021/ol8029214
[16] K. Okano, K. Murata and T.Ikariya, “Stereoselective Syn- thesis of Optically Active Pyridyl Alcohols via Asym- metric Transfr Hydrgenation of Pyridyl Ketones,’’ Tetra- hedron Letters, Vol. 41, No. 48, 2000, pp. 9277-9280. doi:10.1016/S0040-4039(00)01695-6
[17] D. Stark, D. Zala, T. Munch, B. Sonnleitner, I. W. Marison and U. von Stockar, “Inhibition Aspects of the Bio- conversion of L-phenylalanine to 2-phenylethanol by Sa- ccharomyces cervisiae,” Enzyme and Microbial Tech- nology, Vol. 32, No. 2, 2003, pp. 212-223. doi:10.1016/S0141-0229(02)00237-5
[18] J. S. Yadav, S. Nanda, P. Thirupathi-Reddy and A. Bha- skar Rao, “Efficient Enantioselective Reduction of Ke- tones with Daucus carota Root,” Journal of Organic Chemistry, Vol. 67, No. 11, 2002, pp. 3900-3903. doi:10.1021/jo010399p
[19] J. S. Yadav, B. V. Subba Reddy, Ch. Sreelakshmi, G. G. K. S Narayana Kumar and A. Bhaskar-Rao, “Enatioselec- tive Reduction of 2-Substituted Tetrahydropyran-4-ones Using Daucus carota Plant Ccells,” Tetrahedron Letters, Vol. 49, No. 17, 2008, pp. 2768-2771. doi:10.1016/j.tetlet.2008.02.131
[20] A. Ohno, J. Nakai, K. Nakamura, T. Goto and S. Oka, “Reduction by a Model of NAD (P) H. 33. Steric and Electronic Effects on Asymmetric Reduction of 2-acetyl pyridines,” Bulletin of Chemical Society Japan, Vol. 54, No. 11, 1981, pp. 3482-2485. doi:10.1246/bcsj.54.3482
[21] M. Fuji, T. Kamata, M. Okamura and A. Ohno, “A Novel Coenzyme NAD (P)-NAD (P) H Model with Axial Chirality, Its Preparation and Stereo Selectivity,” Journal of Chemical Society, Chemical Communication, No. 12, 1992, pp. 905-906.
[22] B. Jarosz and A. Siewinski, “Enantiospecific Reduction of Prochiral Ketones an Aromatic Type to Optically Active Alcohols in Nigrospora oryzae Culture,” Journal Basic Microbiology, Vol. 36, No. 4, 1996, pp. 245-253. doi:10.1002/jobm.3620360407
[23] K. Uwai, N. Konno, S. Kitamura, S. Ohta and M. Ta- keshita, “Purification and Characterization of Rat Liver Enzyme Catalyzing Stereo Selective Reduction of Acetyl Pyridines,” Chirality, Vol. 17, No. 8, 2005, pp. 494-500. doi:10.1002/chir.20197
[24] P. Soni, G. Kaur, A. K. Chakraborti and U. C. Banerjee, “Candida viswanathii as a Novel Biocatalyst for Stereo- Selective Reduction of Heteroaryl Methyl Ketones: A Highly Efficient Enantioselective Synthesis of (S)-α- (3-pyridyl) Ethanol,“ Tetrahedron: Asymmetry, Vol. 16, No. 14, 2005, pp. 2425-2428. doi:10.1016/j.tetasy.2005.06.018
[25] V. Prelog, “Specifications of the Stereo Specificity of Some Oxidoreductases by Diamond Lattice Sections,” Pure and Applied Chemistry, Vol. 9, No. 1, 1964, pp. 119-130. doi:10.1351/pac196409010119
[26] K. P. Nambiar, D. M. Stauffer P. A. Kolodziej and S. A Benner, “A Mechanistic Basis for the Stereo Selectivity of Enzymatic Transfer of Hydrogen from Nicotinamide Cofactors,” Journal of American Chemical. Society, Vol. 105, No. 18, 1983, pp. 5886-5890. doi:10.1021/ja00356a028
[27] J. G. Quallich and T. M. Woodall, “Enantioselective Oxazaborolidine Reduction of Ketones Containing Hete- roatoms,’’ Tetrahedron Letters, Vol. 34, No. 5, 1993, pp. 785-788. doi:10.1016/0040-4039(93)89012-F
[28] V. Stepaneneko, M. De Jesus, W. Correa, I. Guzma’n, C. Va’zquez, L. Ortiz and M. Ortiz–Marciales, “Spiroborate Esters in the Borane-Mediated Asymmetric Synthesis of Pyridyl and Related Heterocyclic Alcolols,’’ Tetrahedron: Asymmetry, Vol. 18, No. 23, 2007, pp. 2738-2745.
[29] K. Nakamura, Y. Kawai, N. Nakajima and A. Ohno, “Stereochemical Control of Microbial Reduction 17. A Method for Controling the Enantioselectivity of Reduc- tions with Baker’s Yeast,” Journal of Organic Chemis- try, Vol. 56, No. 15, 1991, pp. 4778-4783. doi:10.1021/jo00015a038
[30] K. Ushio, J. Hada, Y. Tanaka and K. Ebara, “Allyl Bro- mide, a Ppowerful Inhibitor against R-Enzyme Activities in Bakers’ Yeast Reduction of Ethyl 3-Oxoalkanoates,” Enzyme and Microbial Technology, Vol. 15, No. 3, 1993, pp. 222-228. doi:10.1016/0141-0229(93)90141-N
[31] M. A. Yu, Y. M. Wei, L. Zhao, L. Jiang, X. -B. Zhu and W. Qi, “Bioconversion of Ethyl4-chloro-3-oxobutanoate by Permeabilized Fresh Brewer’s Yeast Cells in the Pre- sence of Allyl bromide,” Journal of Industrial Microbial Biotechnology, Vol. 3-4, No. 2, 2007, pp. 151-156. doi:10.1007/s10295-006-0179-z
[32] T. Ohkuma, M. Koizumi, M. Yoshida and R. Noyori, “General Asymmetric Hydrogenation of Hetero-Aromatic Ketones,” Organic Letters, Vol. 2, No. 12, 2000, 1749- 1751. doi:10.1021/ol0000814
[33] M. Takeshita, K. Terada, N. Akutsu, S. Yoshida and T. Sato, “Synthesis of Optically Active Hetro Alkylaryl Al- cohols by Baker’s Yeast,” Heterocycles, Vol. 26, No. 12, 1987, pp. 3051-3054. doi:10.3987/R-1987-12-3051
[34] R. Seemayer and M. P. Schneider, “Preparation of Opti- cally Pure Pyridyl-1-ethanols,” Tetrahedron: Asymmetry, Vol. 3, No. 7, 1992, pp. 827-830. doi:10.1016/S0957-4166(00)82175-8
[35] Y. Akakabe, M. Takahashi, M. Kamezawa, K. Kikuchi, H. Tachibana, T. Ohtani and Y.Naoshima, “Biocatalytic Preparation of Chiral Alcohols by Enantioselective Reducetion with Immobilized Cells of Carrot,” Journal of Chemical Society, Perkin Transactions, Vol. 1, 1995, pp. 1295- 1298. doi:10.1039/p19950001295
[36] K. R. K. Prasad and N. N. Joshi, “Oxazaborolidine Cata- lyzed Enantioselective Reduction of 2-Acyl Thiophenes and 2-Acyl furans,” Tetrahedron: Asymmetry, Vol. 8, No. 2, 1997, pp. 173-175. doi:10.1016/S0957-4166(96)00514-9
[37] G. Fantin, M. Fogagnolo, A. Medici, P. Pedrini and S. Poli, “Microbial Oxidation with Bacillus stearothermo- philus: High Enantioselective Resolution of 1-Heteroaryl and l-Aryl Alcohols,” Tetrahedron: Asymmetry, Vol. 4, No. 7, 1993, pp. 1607-1612. doi:10.1016/S0957-4166(00)80367-5
[38] C. Bolm, M. Ewald, M. Felder and G. Schlingloff, “En- antioselective Synthesis of Optically Active Pyridine Derivatives and C2-symmetric2,2’-bipyridines,” Chemische Berichte, Vol. 125, No. 5, 1992, pp. 1169-1160. doi:10.1002/cber.19921250528
[39] J. Uenishi, T. Hiraoka, S. Hata, K. Nishiwaki and O. Yo- nemitsu, “Chiral Pyridines: Optical Resolution of 1-(2- Pyridyl)- and 1-[6-(2,2¢-bipyridyl)] ethanol’s by Lipa- se-Satalyzed Enantioselective Acetylation,” Journal of Organic Chemistry, Vol. 63, No. 8, 1998, pp. 2481-2487. doi:10.1021/jo971521g
[40] M. M. Bradford, “A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein-Dye Binding,” Analytical Biochemistry, Vol. 72, No. 1-2, 1976, pp. 248-254. doi:10.1016/0003-2697(76)90527-3

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.