General access to asymmetric γ-cyclodextrins for gas chromatographic applications by insertion of a selectively modified sugar unit

Abstract

Gas chromatography (GC) using chiral stationary phases (CSPs) based on modified cyclodextrins is the most commonly used technique to quantify enantiomeric purity of synthesized volatile racemic drugs. The fully methylated cyclodextrin derivatives are the most used because of their easy synthesis, their thermal stability and their ability to recognize a wide range of compounds. To complete the background on molecular recognition, we describe a route to access fully characterized new asymmetric cyclodextrins derived from fully methylated ones, thereby directly useful in chiral gas chromatography. The synthesis of these compounds involves a three-step procedure: ring opening of fully methylated cyclodextrins, elongation of the chain with correctly modified monosaccharide derivatives and, finally, macrocyclization to obtain the desired compounds. This strategy is applied to achieve the synthesis of a series of asymmetric γ-cyclodextrins, by insertion of glucopyranosic derivatives. Appropriate selection of the glycosylating reagents during chain elongation and macrocyclization steps allows satisfactory anomeric selectivities to be reached.