Biocatalytic Asymmetric Synthesis
Biocatalytic asymmetric synthesis is a catalytic method commonly known for its popular use in the production of pharmaceuticals. This technology utilizes a biocatalyst, a catalyst of natural origin, to carry out asymmetric synthesis, the selective synthesis of one enantiomeric form of a desired optically active molecule. The use of enzymes in such chemical processes have displayed excellent enantio, chemo, and regioselectivity which is very important for the production of biologically active compounds used in the production of pharmaceuticals and/or natural products. [1][2]
The development of precursor compounds into asymmetric drug products is often carried out through bioreduction, which is considered to be the most potential and competitive industrialization process. [3] The introduction of enzymes to ultimately assist in the bioreduction reaction also influences the chirality of the different possible stereoisomers that are formed in different quantities. A number of enzymes are readily available to be used in the biocatalytic asymmetric synthesis but studies have found that hydrolases, such as lipases, and oxidoreductases, such as alcohol dehydrogenases (ADHs), have shown to be extremely efficient for bioreduction. [4]
Benefits of using Biocatalytic Asymmetric Synthesis Technologies
In comparison to the use of biocatalytic asymmetric synthesis, other methods of pharmaceutical synthesis commonly entail poor enantioselectivity, low conversion, and the formation of byproducts. Other methods also require harsh reaction conditions and the use of toxic metal catalysts. Therefore, having a more efficient method, such as biocatalytic asymmetric synthesis, that can be used to develop highly stereoselective transformations in a sustainable manner that involves the use of much more mild and environmentally friendly reaction conditions has become favoured in industry.[1][5]The synthesis of single enantiomers used by drugs and other intermediates is of great importance as there are a number of side-effects that could arise as well as low effectivity when some drug enantiomers racemates are administered. A popular example of this is the thalidomide scandal that took place in the late 1950’s and early 1960’s, once again outlining the importance of a stereoselective and efficient catalytic method in the world of pharmaceutical production such as biocatalytic asymmetric synthesis.
Studies have found that the generation of waste is dramatically decreased through the use of biocatalytic asymmetric synthesis compared to other conventional methods due to the high atom efficiency under mild operational conditions. Reaction conditions, such as pH, temperature, incubation period and agitation speed can be optimized much more easily compared to other methods which can contribute to the overall effectiveness of this catalytic method. Biocatalysts can also be engineered in a variety of ways, such as substrate walking or introducing mutations, that enables more efficient, economical and environmentally friendly processes used for the manufacture of pharmaceuticals. [2][6]
Pharmaceutical Synthesis
| Precursor | Precursor Derivative | Drug Produced | Treatment/Use [7] |
|---|---|---|---|
| Halohydrins [4] | Imidazoles | Miconazole | Vaginal yeast infections |
| Econazole | Athlete's foot, jock itch, ringworm | ||
| Aryl-substituted Haloethanols | Pronethalol | High blood pressure, angina, arrhythmia, congestive heart disease | |
| Nifenalol | High blood pressure, angina, arrhythmia, congestive heart disease | ||
| Cis-dihydrodiols [5] | Morphian Alkaloids | Codeine | Mild to moderate pain, cough suppressant |
| Morphine | Moderate to severe pain, treatment of diarrhea | ||
| 2-arylpropionic acid [8] | Ibuprofen | Mild to moderate pain, inflammation, fever, complications related to arthritis | |
| Naproxen | Mild to moderate pain, inflammation, fever, complications related to arthritis | ||
| 1-tetralone [3] | Tetralone Rings | Sertraline | Depression, obsessive compulsive disorder, panic attacks, post traumatic stress disorder, social anxiety |
| Etoposide | Cancers (lung, testicular, lymphoma, leukaemia, ovarian) | ||
| Ketones [5] [6] | Chiral Amines | Sitagliptin | Type 2 Diabetes |
| Testosterone | Hypogonadism, delayed puberty, breast cancer | ||
References
- ↑ 1.0 1.1 de María, Pablo; de Gonzalo, Gonzalo; Alcántara, Andrés (2019-09-25). "Biocatalysis as Useful Tool in Asymmetric Synthesis: An Assessment of Recently Granted Patents (2014–2019)". Catalysts. 9 (10): 802. doi:10.3390/catal9100802. ISSN 2073-4344.
- ↑ 2.0 2.1 Taşdemir, Volkan; Kalay, Erbay; Dertli, Enes; Şahin, Engin (2020-05-22). "Bio-catalytic asymmetric synthesis of β-adrenergic receptor blocker precursor: (R)-2-bromo-1-(naphthalen-2-yl)ethanol". Biocatalysis and Biotransformation. 38 (6): 438–444. doi:10.1080/10242422.2020.1768245. ISSN 1024-2422.
- ↑ 3.0 3.1 Kalay, Erbay; Şahin, Engin (2021-05-10). "Biocatalytic asymmetric synthesis of (R)‐1‐tetralol using Lactobacillus paracasei BD101". Chirality. 33 (8): 447–453. doi:10.1002/chir.23318. ISSN 0899-0042.
- ↑ 4.0 4.1 Albarrán-Velo, Jesús; González-Martínez, Daniel; Gotor-Fernández, Vicente (2017-07-10). "Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks". Biocatalysis and Biotransformation. 36 (2): 102–130. doi:10.1080/10242422.2017.1340457. ISSN 1024-2422.
- ↑ 5.0 5.1 5.2 Schrittwieser, Joerg H.; Resch, Verena (2013). "The role of biocatalysis in the asymmetric synthesis of alkaloids". RSC Advances. 3 (39): 17602. doi:10.1039/c3ra42123f. ISSN 2046-2069.
- ↑ 6.0 6.1 Savile, Christopher K.; Janey, Jacob M.; Mundorff, Emily C.; Moore, Jeffrey C.; Tam, Sarena; Jarvis, William R.; Colbeck, Jeffrey C.; Krebber, Anke; Fleitz, Fred J.; Brands, Jos; Devine, Paul N. (2010-07-16). "Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture". Science. 329 (5989): 305–309. doi:10.1126/science.1188934.
- ↑ "MedlinePlus - Health Information from the National Library of Medicine". medlineplus.gov. Retrieved 2021-10-21.
- ↑ Kourist, Robert; María, Pablo Domínguez de; Miyamoto, Kenji (2011-01-10). "Biocatalytic strategies for the asymmetric synthesis of profens – recent trends and developments". Green Chemistry. 13 (10): 2607–2618. doi:10.1039/C1GC15162B. ISSN 1463-9270.
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