title: A kinetic study of product cleavage reactions from the solid phase by a biocompatible and removable cleaving reagent, HCl.
abstract: TFA has been widely used as a cleaving reagent in solid-phase organic synthesis. However, it is difficult to remove from the final product, and it is toxic to various cells. To search for an alternative, we studied the kinetics of HCl cleavage reactions of 18 resin-bound compounds on various linkers. HCl is very easy to remove completely from samples, and the residual HCl does not have a toxic effect in cell assays. Most compounds studied in this work can be easily cleaved using a low concentration of HCl (0.9-2.3%) and the minimal amount of time (60-90 min). Even in the most difficult case, a moderate 8% HCl and an extended time (10-15 h) are enough to cleave the product. Therefore, our kinetic studies establish HCl as a biocompatible, removable, and effective substitute for TFA when final compounds are used for biological screening and drug discovery.
authors.affiliation: St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. Bing.Yan@StJude.org
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.forename: Ranran
authors.initials: R
authors.lastname: Shi
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Tushar
authors.initials: T
authors.lastname: Kshirsagar
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D014269:Trifluoroacetic Acid / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D011108:Polymers; D012996:Solutions; D014269:Trifluoroacetic Acid; D006851:Hydrochloric Acid