Hatice BECEREKLİ, Şaziye Betül SOPACI

Chemo-enzymatic synthesis of chiral precursor molecules with chiral ring hydroxyenone and acetoxyenone structures

Anahtar Kelimeler:

Biotransformation, Lipase, Dehydrogenase, Acetoxygenone, α-hydroxyketon

Chemo-enzymatic synthesis of chiral precursor molecules with chiral ring hydroxyenone and acetoxyenone structures

A biocatalytic transformation has the potential to perform organic reactions that are quite challenging to achieve with synthetic organic chemistry. They also catalyze these reactions with a chemo and enantio selective manner. The discovery and development of new chemoenzymatic methods for the synthesis of these chiral structures is essential to the production of a wide range of bioactive compounds. In this study, two important pharmaceutical precursors were synthesized chemoenzymatically and subjected to biocatalytic conversions with different dehydrogenases. One of these compound is an α-acetoxy enone structure 4-methoxy-2-oxacyclohex-3-enyl acetate and the other is an α-hydroxy ketone 6-hydroxy-3-methoxycycyclohex-2-enone. To obtain these pharmaceutical precursors, 3-methoxy-cyclohex-2-enone was prepared using 1,3-diketone as a starting material. After obtaining this material, α-acetoxy enone was synthesized by chemical acetylation and α-hydroxy ketone prepared by enzymatic deacetylation. The structure of these products was elucidated by NMR analysis. In addition, biocatalytic reduction reactions involving the enzymes galactitol dehydrogenase (GatDH), shikimate dehydrogenase (SDH) and diaphorase were carried out with these products.

Keywords:

Biotransformation, Lipase, Dehydrogenase, Acetoxygenone, α-hydroxyketon,

PDF

___

Ari M. P. (2022). Koskinen Asymmetric Synthesis of Natural Products, John Wiley, USA, ISBN: 978-0-471-93848-4
Bradford, M. M., (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem. 72, 248-251. https://doi.org/10.1016/0003-2697(76)90527-3
Carius, Y., Christian, H., Faust, A., Zander, U., Klink, B.U., Kornberger, P., Kohring, G-W., Giffhorn, F., Scheidig, A. J. (2010). Structural Insight into Substrate Differentiation of the Sugar-metabolizing Enzyme Galactitol Dehydrogenase from Rhodobacter sphaeroides D. J. Biol. Chem. 26, 20006-20007. https://doi.org/10.1074/jbc.M110.113738
Csuk, R. Glanzer, B. I. (1990). Baker’s yeast mediated transformations in organic chemistry, Chem. Rev. 91, 49-97. https://doi.org/10.1021/cr00001a004
Çelik, İ. N., Arslan, F. K., Ramazan, T. U. N. Ç., and Yıldız, İ. (2021). Artificial Intelligence in Drug Discovery and Development. Journal of Faculty of Pharmacy of Ankara University, 45(2), 400-427. https://doi.org/10.1002/med.21764
Demir, A. S., Emrullahoglu, M., (2007). Manganese(III) acetate: A versatile reagent in organic chemistry, Curr. Org. Synth. Bentham Science Publishers B.V. 4, 321-325. https://doi.org/10.2174/157017907781369289
Demir, A.S. Fındık, H. Köse, E., (2004). A new and efficient chemoenzymatic route to both enantiomers of alpha ‘-acetoxy-alpha-methyl and gamma-hydroxy-alpha-methyl cyclic enones, Tetrahedron: Asymm., 15, 777- 781. https://doi.org/10.1016/j.tetasy.2003.12.006
Demir, A. S. Reis, Ö. İğdir, Ç. (2004). Reinvestigation of the synthetic and mechanistic aspects of Mn(III) acetate mediated oxidation of enones, Tetrahedron, , 60, 3427-3432. https://doi.org/10.1016/j.tet.2004.02.039
Demir, A. S., Jeganathan, A. A., (1992). Selective Oxidation Of Alpha,Beta-Unsaturated Ketones At The Alpha’-Position, Synthesis, Elsevier Science, ISBN 978-0-08-052349-1, 235-246.
Faber, K., (1996). Introduction and Background Information, Biotransformations in Organic Chemistry Springer, New York. pp 1–30
Fronza,G., Fuganti,C., Mendozza, M., Rigoni,R., Servia, S., and Zucchi,G., (1996). Stereochemical aspects of flavour biogeneration through baker’s yeast mediated reduction of carbonyl-activated double bonds. Pure & Appl. Chem., 68, 11, 2065-2071, https://doi.org/10.1351/pac199668112065
Heiba E. I., Dessau R., and Rodewald M., (1974). Oxidation by Metal Salts. X. One-step synthesis of Gamma.-lactones from olefins, J. Am. Chem. Soc., 96, 7977-7981. https://doi.org/10.1021/ja00833a024
Heiba, E. I., Dessau, R. M. (1974) Oxidation by metal salts XI. The Formation of Dihydrofuranes, J. Org.Chem, 39, 3456-3457. ISSSN 0022-3263
Huang Y., and Hayashi T., (2022). Chiral Diene Ligands in Asymmetric Catalysis, Chem. Rev., 122, 18, 14346-14404, https://doi.org/10.1021/acs.chemrev.2c00218
Kataoka, M., Kita, K., Wada, M., Yasohara, Y., Hasagawa, and J. Shimizu. A school-based mental health program for traumatized Latino immigrant children, S. App. Microb. Biotech. (2003), 62, 437-445. https://doi.org/10.1097/00004583-200303000-00011
Kongkona S, Abiram K., R., Ponnusamy S.K. , Sunita V., Mohideen N. , Rashmi L., Jenet G., Vinoth K.V., (2021), Recent advances in biotransformation of 5-Hydroxymethylfurfural: challenges and future aspects. J. Chem. Technol. Biotechnol. 97: 409-419, https://doi.org/10.1002/jctb.6670
Mane, S., (2016). Analytical Methods Racemic Drug Resolution: A Comprehensive Guide, Chemistry, Doi:10.1039/ C6AY02015
Mindt M., Kashkooli A. B. , Suarez-Diez M. , Ferrer L. , Jilg T. , Bosch D. , Martins dos Santos V. , Wendisch F. V. and Cankar K., (2022). Production of indole by Corynebacterium glutamicum Microbial Cell Factories for Flavor and Fragrance Applications. Microbial Cell Factories Volume 21, Article number: 45. https://doi.org/10.1186/s12934-022-01771-y
Noyori, R., Suzuki, M. (2006). Angewandte, The Journal of Physical Chemistry B. 96, 854-882. https://doi.org/10.1021/ja064500p
Schoepe, J., Niefind, K., Chatterjee, S. and Schomburg, D. (2006) Cloning, expression, purification and preliminary crystallographic characterization of a shikimate dehydrogenase from Corynebacterium glutamicum Acta Cyristallographica 62, 635- 637. https://doi.org/10.1107/S1744309106017805
Sachin M., (2016). Racemic drug resolution: a comprehensive guide, Analytical Methods, Royal Society of Chemistry, Issue 42. https://doi.org/10.1039/C6AY02015A
Tanyeli, C., Özdemirhan D., Ezen, B. (2002) ROMP-Polymers in Asymmetric Catalysis: The Role of the Polymer Backbone, Tetrahedron Asymm. Mathematical & Physical Sciences, Scholarly Journals, Elsevier, 58, 9983-9988. https://doi.org/10.1002/1615-4169
Yinhua H., and Tamio H., (2022). Chiral Diene Ligands in Asymmetric Catalysis, Chem. Rev. 2022, 122, 18, 14346-14404 Publication Date: August 16, https://doi.org/10.1021/acs.chemrev.2c00218
Zelinski, T.; Kula, M. R. (1994). A kinetic study and application of a novel carbonyl reductase isolated from Rhodococcus erythropolis, Bioorg. Med. Chem. Bioorganic & Medicinal Chemistry Letters, 2, 421-428. https://doi.org/10.1016/0968-0896(94)80010-3
Zhuozhuo He, Lingzi Peng & Chang Guo, (2022). Catalytic stereodivergent total synthesis of amathaspiramide D, Nature Synthesis volume 1, pages 393-400. https://doi.org/10.1038/s44160-022-00063-y