Advances and applications of chiral resolution in pharmaceutical field

Abstract

The attention to chiral drugs has been raised to an unprecedented level as drug discovery and development strategies grow rapidly. However, separation of enantiomers is still a huge task, which leads to an increasing significance to equip a wider range of expertise in chiral separation science to meet the current and future challenges. In the last few decades, remarkable progress of chiral resolution has been achieved. This review summarizes and classifies chiral resolution methods in analytical scale and preparative scale systematically and comprehensively, including crystallization‐based method, inclusion complexation, chromatographic separation, capillary electrophoresis, kinetic resolution, liquid–liquid extraction, membrane‐based separation, and especially one bold new progress based on chiral‐induced spin selectivity theory. The advances and recent applications will be presented in detail, in which the contents may bring more thinking to wide‐ranging readers in various professional fields, from analytical chemistry, pharmaceutical chemistry, natural medicinal chemistry, to manufacturing of drug production.

Recent Advances in Separation and Analysis of Chiral Compounds

“…Compared with chromatographic separation techniques that are usually performed in an analytical scale, membrane separation has greater potential for large preparative scale separation (more than kilogram level) in pharmaceutical and chemical engineering fields. 114,115 Conventional chiral membranes are prepared from polysaccharides (chitosan and cellulose), sodium alginate, poly-(substituted acetylene), poly(amino acids), and lipids. 116−119 Industrial application for most chiral membranes is still difficult because of insufficient enantioselectivity under high flux following the facilitated transport mechanism.…”

“…Membranes with enantioselective permeability are another common separation media. Compared with chromatographic separation techniques that are usually performed in an analytical scale, membrane separation has greater potential for large preparative scale separation (more than kilogram level) in pharmaceutical and chemical engineering fields. , Conventional chiral membranes are prepared from polysaccharides (chitosan and cellulose), sodium alginate, poly­(substituted acetylene), poly­(amino acids), and lipids. − Industrial application for most chiral membranes is still difficult because of insufficient enantioselectivity under high flux following the facilitated transport mechanism. Because the performance of membranes essentially depends on different interactions between enantiomers and chiral discriminating units of membranes during transport process, the exploration of new chiral materials with high selectivity, excellent permeability, good stability, and long-time operation has been the main focus in recent years, represented by improved polymers, porous crystalline materials, carbon nanomaterials, and micro/nanochannels. − These up-to-date membrane materials have continued to grow for chiral separation in the past two years.…”

Air‐tolerant upconverted circularly polarized luminescence enabled by confined space of chiral micelle

“…Circularly polarized luminescence (CPL) has attracted tremendous concern from scientists in related fields because of its wide application in various domains 1–9 . The study on CPL is not only important for the enantioselectively physiological mechanisms and phenomena in organisms but also significant to the design of chiral materials in a variety of research domains 10–18 . CPL materials have the capacity to emit left‐handed or right‐handed circularly polarized light, whose properties can be typically defined by a luminescence dissymmetry factor ( g lum ), 19 and calculated by the follow equation: where I L and I R represent the emission intensity of the left‐handed and right‐handed CPL, respectively.…”

“…[1][2][3][4][5][6][7][8][9] The study on CPL is not only important for the enantioselectively physiological mechanisms and phenomena in organisms but also significant to the design of chiral materials in a variety of research domains. [10][11][12][13][14][15][16][17][18] CPL materials have the capacity to emit left-handed or right-handed [This article is part of the Special issue: Chiral Materials. See the first articles for this special issue previously published in Volumes 34:12, 35:2, 35:3, 35:4 and 35:5.…”

Enantioselective Transformations in the Synthesis of Therapeutic Agents

“…3 In drug discovery, the traditional and dominant approach to enantiomerically pure pharmaceutical molecules relies on chemical resolution of a racemic mixture. 4 Nevertheless, such a tactic is not realistic and economical in industrial production at the expense of sacrificing half the amount of material in most cases.…”