Biocatalysis: A smart and green tool for the preparation of chiral drugs

Abstract

Over the last decades, biocatalysis has achieved growing interest thanks to its potential to enable high efficiency, high yield, and eco-friendly processes aimed at the production of pharmacologically relevant compounds. Particularly, biocatalysis proved an effective and potent tool in the preparation of chiral molecules, and the recent innovations of biotechnologies and nanotechnologies open up a new era of further developments in this field. Different strategies are now available for the synthesis of chiral drugs and their intermediates. Enzymes are green tools that offer several advantages, associated both to catalysis and environmentally friendly reactants. Specifically, the use of enzymes isolated from biological sources or of whole-cell represents a valuable approach to obtain pharmaceutical products. The sustainability, the higher efficiency, and cost-effectiveness of biocatalytic reactions result in improved performance and properties that can be translated from academia to industry. In this review, we focus on biocatalytic approaches for synthesizing chiral drugs or their intermediates. Aiming to unveil the potentialities of biocatalysis systems, we discuss different examples of innovative biocatalytic approaches and their applications in the pharmaceutical industry.

Discovery, Structure, and Mechanism of the (R, S)-Norcoclaurine Synthase for the Chiral Synthesis of Benzylisoquinoline Alkaloids

“…Its profound implications in pharmacy, life sciences, and physics have spurred interest in understanding its origins, formation, functions, and effect on the three-dimensional nature of human society . However, synthesizing chiral molecules, especially those with multiple chiral centers, poses considerable challenges. , For instance, commercial chemical syntheses of analgesics such as morphine and codeine, along with their subclasses, have been hindered owing to the five inherent asymmetric carbons. − Plants are deemed to be the greatest chemists and various compounds of particular configuration were created, whereas the underlying mechanisms of plants to synthesize chiral-specific compounds remain largely undeciphered. One representative example is benzylisoquinoline alkaloids (BIAs), a diverse group of natural compounds with significant pharmacological activities and biological effects. , While most BIAs in nature are recognized as ( S )-enantiomers, numerous ( R )-enantiospecific BIAs, including morphine and its derivatives, are also abundant in certain species such as opium poppy and lotus (Nelumbo nucifera). , Considering that chiral-specific BIAs have attracted continuous attention for their role in drug discovery and development, understanding of underlying mechanisms of chiral control is helpful in developing a biotechnological strategy for their production.…”

“…1 However, synthesizing chiral molecules, especially those with multiple chiral centers, poses considerable challenges. 2,3 For instance, commercial chemical syntheses of analgesics such as morphine and codeine, along with their subclasses, have been hindered owing to the five inherent asymmetric carbons. 4−6 Plants are deemed to be the greatest chemists and various compounds of particular configuration were created, whereas the underlying mechanisms of plants to synthesize chiral-specific compounds remain largely undeciphered.…”

Wireless electromechanical enantio‐responsive valves

“…11 For example, for biological systems, a specific pharmaceutical compound can be designed for a defined biological receptor, where chirality is used to tune the nature of the interaction. 12 As such, enantiomeric interactions ultimately control and perturb biological functions; thus, enantiorecognition is of tremendous importance in biological systems. Although different spectroscopic methods have [This article is part of the Special Issue: Chirality Materials.…”

“…Due to their numerous applications in medicine, chemistry or biochemistry, chiral molecules have gained considerable attention 11 . For example, for biological systems, a specific pharmaceutical compound can be designed for a defined biological receptor, where chirality is used to tune the nature of the interaction 12 . As such, enantiomeric interactions ultimately control and perturb biological functions; thus, enantiorecognition is of tremendous importance in biological systems.…”

Chiral Recognition of Chiral (Hetero)Cyclic Derivatives Probed by Tetraaza Macrocyclic Chiral Solvating Agents via 1H NMR Spectroscopy

“…Nuclear magnetic resonance (NMR) spectroscopy plays an increasingly important role as a fast and powerful analytical tool in the field of chiral recognition, including the assignment of absolute configuration of chiral molecules and determination of enantiomeric excess of chiral compounds. − These parameters constitute important and fundamental characterization data in many related research areas, such as in the evaluation of asymmetric synthetic , and natural products, , as well as in fields such as food science − and chiral materials. , In particular, in chiral pharmaceutical chemistry, different enantiomers of chiral drugs have different biological and pharmaceutical activities, with one producing beneficial outcomes to combat human diseases, whereas the other one may have a detrimental, if not toxic effect to health. − Over the past decade, NMR spectroscopy, assisted by the use of chiral oriented solvents, , and especially chiral solvating agents (CSAs) as chiral auxiliaries, has received considerable attention in chiral recognition − due to several advantages, such as fast and convenient operation, accurate and reliable measurement, low sample consumption, and need for small amounts of deuterated solvent. In addition, multiple field windows are often available for observing split proton signals by 1 H NMR spectroscopy, an ubiquitous technique available in nearly all chemical and related laboratories. , However, developing highly sensitive, effective, and versatile chiral auxiliaries, especially CSAs, remains a challenging undertaking.…”