Chemo-Enzymatic Synthesis of Enantiopure β-Antagonist (S)-Betaxolol
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of 1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol (5a) and 1-bromo-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol (5b)
2.1.1. Synthesis of 1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol (5a)
2.1.2. Synthesis of 1-bromo-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol (5b)
2.2. CALB Catalyzed Kinetic Resolution of 1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol (5a) and 1-bromo-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol (5b)
2.3. Synthesis of (S)-betaxolol ((S)-7)
3. Materials and Methods
3.1. Chemicals and Solvents
3.2. TLC-Analyses and Column Chromatography
3.3. Enzyme Preparations
3.4. NMR Analyses
3.5. Optical Rotation
3.6. Chiral HPLC Analyses
3.7. Liquid Chromatography-Mass Spectroscopy (LC-MS)
3.8. Mass Spectrometry Analysis
3.9. Synthesis Protocols
3.9.1. 4-(2-(Cyclopropylmethoxy)ethyl)phenol (2)
3.9.2. 2-((4-(2-(Cyclopropylmethoxy)ethyl)phenoxy)methyl)oxirane (3)
3.9.3. 2-(4-(Oxiran-2-ylmethoxy)phenyl)ethan-1-ol (4)
3.9.4. 1-Chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol (5a)
3.9.5. 1-Bromo-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol (5b) Correct Procedure
3.9.6. Synthesis of 1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-yl butanoate (6a)
3.9.7. Synthesis of Racemic Betaxolol (7)
3.9.8. CALB Catalyzed Kinetic Resolution of 1-chloro-3-(4-(2-(cyclopropylme-thoxy)ethyl)phenoxy)propan-2-ol (5a)
3.9.9. CALB catalyzed Kinetic Resolution of 1-bromo-3-(4-(2-(cyclopropylme-thoxy)ethyl)phenoxy)propan-2-ol (5b)
3.9.10. Synthesis of (S)-betaxolol ((S)-7) from (R)-5a
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Troøyen, S.H.; Jacobsen, E.E. Chemo-Enzymatic Synthesis of Enantiopure β-Antagonist (S)-Betaxolol. Catalysts 2022, 12, 1645. https://doi.org/10.3390/catal12121645
Troøyen SH, Jacobsen EE. Chemo-Enzymatic Synthesis of Enantiopure β-Antagonist (S)-Betaxolol. Catalysts. 2022; 12(12):1645. https://doi.org/10.3390/catal12121645
Chicago/Turabian StyleTroøyen, Susanne Hansen, and Elisabeth Egholm Jacobsen. 2022. "Chemo-Enzymatic Synthesis of Enantiopure β-Antagonist (S)-Betaxolol" Catalysts 12, no. 12: 1645. https://doi.org/10.3390/catal12121645