Chirality and Drug Discovery

Abstract

The relationship between chirality and biological is extremely important to the pharmaceutical and biopharmaceutical areas as evidenced by the number of single enantiomer new drugs that have been developed and approved. This article covers several areas of importance for the design and synthesis of novel small molecules drugs to medicinal chemists. The chirality includes atropisomers and the impact of these chiral molecules and their biological implications are discussed. In addition to chirality at carbon, examples of chiral compounds involving chirality at non‐carbon atoms are included. A section titled “chiral switch” covers recent drug development and marketed of single enantiomers.

Homochiral Optical Fibers Coated with Nanoscale Films of Metal–Organic Frameworks and Double-Plasmonic Ag and Au for In Situ Enantioselective Detection

“…In medical applications, the efficiency and suitability of chiral organic molecules are determined by their enantiomeric configuration. , In many cases, one enantiomer can serve as an effective drug, while its mirror-image counterpart may be ineffective, potentially hindering the drug’s activity or even being toxic. ,− Thus, the recognition of molecular chirality and enantio-purity is an important task in the pharmacological industry and in many related fields. , Today, analytical methods such as chiral chromatography, circular dichroism spectroscopies, or, in some particular cases, nuclear magnetic resonance are commonly used for enantioselective analysis and estimation of enantiomer excess. − These methods generally benefit from high analysis accuracy and low detection limits. However, they have several disadvantages: they need expensive, bulky equipment, specially trained staff, complex procedures of sample preparation, and are time-demanding.…”

Cyclocondensation reactions of racemic diastereomers of dimethyl-2-oxocyclohexanepropionic acids with (R)-phenylglycinol: access to both enantiomers of dimethylcis-decahydroquinolines

“…The search for new and efficient methodologies for the preparation of optically pure compounds continues to be an important issue in synthetic organic chemistry, particularly in the context of the synthesis of drugs and bioactive products. 1 In this respect, the development of practical synthetic methods for the generation of multiple stereocenters with high diastereo- and enantioselectivity in a single synthetic step has long constituted a challenging goal for organic chemists.…”

Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester

“…Knowing the precise structure is also of pivotal importance to understand the mechanisms of action and to design derivatives with best pharmacological performance [1,2]. Many bioactive natural products are chiral compounds produced by living organisms as single stereoisomers whose artificial enantiomers often result less active, if not noxious [3,4]. From an economic and environmental point of view, a sustainable industrial synthesis of these metabolites should require highly efficient and selective reactions so as to reduce the number of steps, simplify the purification procedures and consequently reduce waste formation and energy costs [5].…”