The preparative chromatographic enantioseparation of a racemic morphanthridine analog on a chiral stationary phase

Abstract

Key WordsColumn liquid chromatography Preparative scale separations Chiral stationary phase Enantiomer separation Morphanthridine analog SummaryThe preparative chromatographic enantioseparation of a chiral morphanthridine analog has been performed on an analytical column using amylose-tris(3,5-dimethylphenylcarbamate) as chiral stationary phase. The racemate (100 mg) was resolved to baseline within 15 min. This paper describes the development of the method, estimation of the capacity of the chiral stationary phase and discusses the potential of the chromatography if performed under preparative conditions. From the resuits and calculations presented it seems likely that the resolution of 70 tons year -1 could easily be achieved on 30 kg of stationary phase with a mobile-phase consumption of only 720 L day -1. resolution of which on a CSP seemed likely to be highly effective. It is the purpose of this communication to introduce this enantioseparation on a commercially available CSP and to discuss the potential of the chromatography if performed under preparative conditions. ExperimentalA Hewlett-Packard 1050 HPLC system was used for chromatography. Chiralpak-AD was purchased from Daicel Chemical Industries (Tokyo, Japan). The solvents used for the preparation of the mobile phases were LiChrosolv grade from Merck (Darmstadt, Germany). The mobile phase composition and chromatographic conditions are given in the captions to Figures 2 and 3.Dead time (tm) was estimated by use of 1,3,5-tri-tertbutylbenzene. The capacity factor, k, was calculated from k = (tr -tm)/tm, the enantioselectivity, a, from a = k2/kl and the resolution factor, R, from R = 1.18(t2 -tl)/(Wl(0.5) + W2(0.5)), where kl and k2 and tl and t2 refer to the capacity factors and retention times of the first and second eluted enantiomers and Wl(0.5) and W2(0.5) are the corresponding peak widths at half-height.

Trends in Preparative HPLC

“…Given the good solubility of a racemic morphanthridine in the mobile phase and the large separation factor, the author decided to estimate the capacity of the CSP for the given separation [33]. The injection amount systematically increased to estimate the final value for which a baseline separation could be observed.…”

Recent applications of stereoselective chromatography

“…This can be done on an analytical column as in the case of a morphantridine analog separated on Chirapak AD column with hexane/2-propanol (85:15 v/v) mobile phase at a flow rate of 0.5 ml/min at 40°C, using UV detection at 290 nm; 100 mg of racemate dissolved in 250 ml (loop volume) of hexane-2-propanol mixture (1:1, v/v) was injected and baseline separation was accomplished within 15 min. 126 The same column was used for preparative enantioseparations of hydrochlorides of propranolol and thioridazine under supercritical fluid chromatography conditions (mobile phase of CO 2 /MeOH mixtures). The amounts of racemates separated on a 25 cm 1 cm I.D.…”

Chiral Separations

“…Another derivatized polysaccharide CSP was used to enantioresolve a chiral morphanthridine analogue. This method used amylose tris(3,5-dimethylphenyl carbamate) as a CSP (124). The first direct enantioseparation of gossypol was reported on a CSP consisting of cellulose tris(3,5-dimethylphenyl carbamate) coated onto microporous aminopropylsilica (125).…”