A novel baker’s yeast-mediated microwave-induced reduction of racemic 3-Keto-2-Azetidinones: Facile entry to optically active hydroxy β-lactam derivatives

Optically active hydroxy β-lactams are important compounds for the synthesis of many other molecules in chiral forms [1]. They are also important components of β-lactam antibiotics (a class of medicines that includes penicillins, cephalosporins, carbapenems, and monobactams).  A team of researchers at Prince Mohammad Bin Fahd University in Al Khobar led by Professor Bimal Krishna Banik has been working for some time on β-lactam chemistry. Professor Banik’s team has recently published their report on the reduction of 3-keto β-lactams to an unequal distribution of chiral 3-hydroxy β-lactams derivatives. They have done this through the use of microwaves.

Microwave-induced reactions have demonstrated numerous applications in the synthesis of organic compounds [2]. Microwave irradiation and enzymatic catalysis synergistically raise the reaction rate significantly. Several reports have explained the biodegradation of toxic organic pollutants using different enzymes from bacteria, fungi, and plants. However, many applications of biochemical synthesis by microwave-induced reactions await discovery.

Banik’s team investigated chiral reduction of activated keto esters to their chiral β-hydroxy esters with both free and immobilized baker’s yeast (Saccharamyces Cerevisiae, type 3) [3, 4].  Numerous organic solvents were also used in bio-catalytic processes [5-8]. Glycerol was also employed for a few enzymatic methods [9].

In their recent study, baker's yeast was used to reduce the keto functionality of α-keto-β-lactam in glycerol under microwave irradiation. Glycerol is a high boiling polar solvent and ideally suited for our microwave-induced reactions in open vessels. Two hydroxyl compounds were produced in a 3:1 ratio in 65% yield. NMR data of these compounds indicated their cis and trans-configuration. The NMR data of the optically active acetates in the presence of the chiral shift reagent confirms that the optically active acetates obtained from the reduction were virtually optically pure.

Optically pure cis β-lactam that is present in Taxol and Taxotere and trans β-lactam can be prepared in this way [3, 10]. The biocatalytic methods described here should be applicable to 3-keto-2-azetidinones with various aromatic and non-aromatic groups at positions 1 and 4.

“The present finding opposes numerous speculations that the function of enzymes is temperature dependent.” says Banik. “Our study confirms that baker’s yeast can be employed at relatively high temperature in microwave-induced process and the outcome of the process can be highly significant in producing mixtures of bioactive compounds.” Their research has been published in the journal, Current Organocatalysis.

Acknowledgements:

Bimal Krishna Banik gratefully acknowledges the financial support for this project from the USA NIH and USA NCI.   

Authors:

Aparna Das,¹ Ram Naresh Yadav,² and Bimal Krishna Banik^3*  

¹Department of Mathematics and Natural Sciences, College of Sciences and Human Studies, Prince Mohammad Bin Fahd University, Al Khobar 31952, Kingdom of Saudi Arabia; ²Department of Chemistry, Faculty of Engineering & Technology, Veer Bahadur Singh Purvanchal University, Jaunpur Uttar Pradesh; ³Department of Mathematics and Natural Sciences, College of Sciences and Human Studies, Deanship of Research, Prince Mohammad Bin Fahd University, Al Khobar 31952, Kingdom of Saudi Arabia; Email: bimalbanik10@gmail.com; bbanik@pmu.edu.sa

References:

1. Banik, B.K.; Manhas, M.S.; Bose, B.K. EnantiopureHydroxy β-Lactams via Glycosylation. Tetrahedron Lett., 1997, 38 (29), 5077-5080.
2. (a) Banik, B.K.; Bandyopadhyay, D. Advances in Microwave Chemistry. Taylor & Francis, UK and USA: CRC Press, 2019; (b) Yadav, R.N.; Banik, I.; Banik, B.K. Montmorillonite-Catalyzed Glysosylation of Alcohols With Glycals Derived From Galactose and Glucose Under Microwave-Induced Reactions. J. Ind. Chem. Soc., 2018, 95, 1385-1387; (c) Mahato, A.; Sahoo, B.M.; Banik, B.K.; Mohanta, B.C. Microwave-assisted Synthesis: Paradigm of Green Chemistry. J. Ind. Chem. Soc., 2018, 95, 1327-1339.
3. Brieva, R.; Grich, J.A.; Sih, C.J. Chemoenzymic synthesis of the C-13 side chain of taxol: optically active 3-hydroxy-4-phenyl. beta.-lactam derivatives. J. Org. Chem., 1993, 58 (5), 1068-1075.
4. Forro, E.; Paal, T.; Tasnadi, G.; Fulop, F. A New Route to Enantiopure β-Aryl-Substituted β-Amino Acids and 4-Aryl-ubstituted β-Lactams through Lipase-Catalyzed Enantioselective Ring Cleavage of β-Lactams. Adv. Synth. Catal., 2006, 348 (7-8), 917-923.
5. Qun, J.; Shanjing, Y.; Lehe, M. Tolerance of immobilized baker’s yeast in organic solvents.

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2. Medson, C.; Smallridge, A.J.; Trewhella, M.A. The stereoselective preparation of β-hydroxy esters using a yeast reduction in an organic solvent. Tetrahedron: Asymmetry, 1997, 8 (7), 1049-1054.
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4. Wolfson, A.B.; Dlugy, C.; Shotland, Y. Glycerol as a green solvent for high product yields and selectivities. Environ. Chem. Lett., 2006, 5, 67-71. 
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