Enantioseparation characteristics of tadalafil and its intermediate on chitin derived chiral stationary phases

Abstract

Due to the low solubility and swelling properties of chitin bis(arylcarbamate) in most organic solvents, the chiral stationary phases (CSPs) prepared from chitin derivatives can be analyzed with a wide range of solvents. In order to develop new CSPs of chitin derivatives with halogen groups, chitin was derivatized with three different phenyl isocyanates to obtain chitin bis(4-trifluoromethoxyphenylcarbamate), chitin bis(3-chloro-4-methylphenylcarbamate) and chitin bis(4-chloro-3-trifluoromethylphenylcarbamate). Then, the three chitin derivatives were coated on macroporous 3-aminopropyl-functionalized silica gel to obtain three CSPs 1-3 respectively. These CSPs showed good enantioseparation capabilities towards tadalafil and its intermediate. Therefore, these CSPs are potentially applied for the enantioseparation and determination of tadalafil and its intermediate. It was also found that the retention times of some enantiomers were prolonged in the presence of their diastereoisomers or structural analogues and as a result, the resolution was improved to some extent. Hence, in the enantioseparation of a compound with two chiral centers, the resolution is hopefully improved by adding a diastereoisomer or a structural analogue.

Recent development trends for chiral stationary phases based on chitosan derivatives, cyclofructan derivatives and chiral porous materials in high performance liquid chromatography

“…Eluent: (A) n‐hexane/ethanol (80:20, v/v) and (B) n‐hexane/ethanol (90:10, v/v). Reproduced with permission from …”

“…More systematic studies including the influence of substituents and the tolerance to various organic solvents on the enantioseparation of many novel CSPs based on chitosan derivatives using highly deacetylated chitosan as a starting material have been reported by the Bai group. For example, a series of chitosan alkyl amide and alkyl urea derivatives were prepared upon introducing an alkyl group, such as cyclobutyl [27], isobutyryl [28][29][30], n-octyl [31] and n-pentyl [32], at the 2-position of chitosan, and the chiral recognition ability and the solvent tolerance of these chitosan derivatives bearing the same phenylcarbamate groups at the Reproduced with permission from [26] 3-and 6-position investigated ( Figure 2). It was observed that the chiral recognition performance of these coated-type CSPs was significantly influenced by the nature (e.g., electronwithdrawing and electron-donating properties), position, and number of substituents on the phenyl moieties of the chitosan derivatives and the eluent's composition.…”

Chiral Stationary Phases for Liquid Chromatography Based on Chitin- and Chitosan-Derived Marine Polysaccharides

“…Following the same strategy, and aiming the enantioseparation of tadalafil and its intermediates, Zhang et al, synthesized new chitin bis-arylcarbamates, specifically chitin 3-chloro-4-methyl-(18), 4-trifluoromethoxy-(19) and 4-chloro-3-trifluoromethyl- (20) phenylcarbamates (Table 1) [56]. The three chitin derivatives were coated on macroporous 3-aminopropyl silica and the obtained CSPs were successful in the enatioresolution of all tested analytes [56].…”

“…The best chromatographic result was achieved for flavanone with α and Rs values of 4.70 and 4.33, respectively, using a mixture of hexane/2-propanol 80:20 as mobile phase [65]. In recent studies (2016), Tang et al, prepared several bis-phenylcarbamate derivatives in which the amine moiety of chitosan was modified by an isobutyrylamide moiety (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57) [66,67]. The synthesized chitosan derivatives were coated on aminopropyl silica resulting in a series of new CSPs for LC.…”

Chiral stationary phases based on chitosan bis(4-methylphenylcarbamate)-(alkoxyformamide)

“…Moreover, there is a helix in chitin suprastructure , and this structural feature is critical for polysaccharide derivatives to exert the function in chiral separation . Thus, chitin and chitosan were once derivatized and the resulting products were used as chiral selectors for chiral stationary phases (CSPs) . In addition, according to the reports , carbamylated chitin/chitosan derivatives are difficultly dissolved in common organic solvents, thus possibly being highly tolerable to mobile phases that consist of various organic solvents.…”