Solution‐phase synthesis and evaluation of tetraproline chiral stationary phases

Abstract

A protocol was developed for the solution-phase synthesis of multigram amounts of two 9-fluorenylmethoxycarbonyl (Fmoc)-protected tetraproline peptides. These tetraproline peptides were then attached to amino derivatized silica gel. The replacement of the Fmoc group with the trimethylacetyl group lead to two tetraproline chiral stationary phases (CSPs). A comparison of the chromatographic behavior of these two solution-phase-synthesized tetraproline CSPs with that prepared by stepwise solid-phase synthesis revealed that all three had similar chromatographic performance for resolving 53 model analytes. This suggests that the solution-phase synthesis of oligoprolines, which allows for the specific benefits of good batch reproducibility, selector homogeneity, and possibly low cost, is a feasible alternative to the solid-phase synthesis of oligoproline CSPs.

Enantiomeric Recognition of Racemic 4‐Aryl‐1,4‐dihydropyridine Derivatives via Chiralpak AD‐H Stationary Phases

“…Although enantiomerically pure 1,4‐dihydropyridines have great biological importance, a general methodology for resolving the enantiomers and then evaluating them remains difficult. High‐performance liquid chromatography (HPLC) separation of enantiomers on chiral stationary phases (CSPs) is a convenient and accurate method for the determination of the enantiomeric purity of chiral compounds . The direct resolutions of dihydropyridine enantiomers using a CSP in LC are now reaching an advanced stage .…”

Enantiomeric Separation of Racemic 4‐Aryl‐1,4‐Dihydropyridines and 4‐Aryl‐1,2,3,4‐Tetrahydropyrimidines on a Chiral Tetraproline Stationary Phase

“…Hexanes (from Fisher Scientific) were a mixture of hexanes (86.1% n ‐hexane, 9.7% methylcyclopentane, 4.2% various methylpentanes). The Pro4CSP chiral stationary phase was prepared previously in our lab . The Pro4CSP chiral stationary phase was packed into a 50 mm × 4.6 mm HPLC column following the conventional high‐pressure slurry packing method (surface loading 0.42 mmol/g).…”

“…Our group has developed a new class of promising chiral stationary phases based on proline (Pro) oligomers, which have broad enantioselectivity in the normal‐phase mode. Despite significant progress in chiral stationary phase development over the past decade, chiral recognition mechanisms are still not well understood.…”

Study of stereomeric peptoid chiral stationary phases containing different chiral side chains

“…However, with the increasing number of racemates which need to be resolved, novel valuable CSPs are still demanded. For example, CSPs based on oligoproline [9][10][11][12], cyclofructan [13][14][15][16], polymeric diamine derivatives [17][18][19] and zwitterionic cinchona alkaloid [20,21] attract much attention recently.…”