title: From analytical methods to large scale chiral supercritical fluid chromatography using chlorinated chiral stationary phases.
abstract: While traditional non-chlorinated Cellulose- and Amylose-derivatized phases have been used successfully in supercritical fluid chromatography (SFC) to resolve a broad variety of chiral compounds, some chiral pharmaceutical compounds are not well resolved on these traditional chiral stationary phases (CSP) due to the lack of chiral selectivity. Since there are no universal CSP to resolve all chiral compounds, chlorinated CSP can be complementary to the non-chlorinated CSP. Chlorinated CSP such as 4-Chloro-3-methylphenyl-carbamatecellulose (Lux-Cellulose-4), 3-Chloro-4-methylphenyl-carbamatecellulose (Lux-Cellulose-2), 5-Chloro-2-methylphenyl-carbamateamylose (Lux-Amylose-2) and immobilized 3,5-dichlorophenyl-carbamatecellulose (Chiralpak IC) have provided a range of chiral recognition mechanisms which have allowed the authors to successfully achieve chiral SFC resolution on several structurally diverse compounds, which are not well resolved in the non-chlorinated CSP. In addition, chlorinated Lux-Cellulose-4, Chiralpak IC and Lux-Amylose-2 have enabled us to utilize non-alcohol solvents as sample diluents and as co-solvents to significantly improve compound solubility and selectivity. This article will discuss the challenges associated with several SFC applications on both coated and immobilized chlorinated CSP to deliver high-quality drug candidates in large quantity. The use of dichloromethane in both sample preparation and as co-solvent in CO2 to increase sample solubility will be presented in preparative example #2 and #3.
authors.affiliation: Research and Development, Bristol-Myers Squibb Co., Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA. Electronic address: dauh-rurng.wu@bms.com.
authors.forename: Dauh-Rurng
authors.initials: DR
authors.lastname: Wu
authors.affiliation: Research and Development, Bristol-Myers Squibb Co., Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA.
authors.forename: Shiuhang Henry
authors.initials: SH
authors.lastname: Yip
authors.affiliation: Research and Development, Bristol-Myers Squibb Co., Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Research and Development, Bristol-Myers Squibb Co., Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Sun
authors.affiliation: Research and Development, Bristol-Myers Squibb Co., Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Mathur
mesh_terms: D000688:Amylose / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D025924:Chromatography, Supercritical Fluid / Q000379:methods; D054879:Halogenation; D008752:Methylene Chloride; D004364:Pharmaceutical Preparations / Q000302:isolation & purification*; D012995:Solubility; D012997:Solvents; D013237:Stereoisomerism
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D008752:Methylene Chloride; D002482:Cellulose; D000688:Amylose
keywords: Chiral separations; Chlorinated chiral stationary phases; Drug discovery; Large scale; Supercritical fluid chromatography