erythro-1-Naphthyl-1-(2-piperidyl)methanol: synthesis, resolution, NMR relative configuration, and VCD absolute configuration.

The erythro isomer of 1-naphthyl-1-(2-piperidyl)methanol 4, an efficient chiral modifier for asymmetric heterogeneous hydrogenation, was obtained as the major isomer (95%) in two steps while the threo isomer can be obtained as the major isomer (67%) in three steps. erythro-4 and threo-4 were resolved on a CHIRALCEL OD-RH column. It has been shown by VCD that the diastereomer determined as the erythro by NMR was indeed the erythro and that the first eluted (-)-enantiomer on CHIRALCEL OD-R or -RH columns has the (1R,2S) configuration. The VCD studies identify the presence of at least five conformers in CDCl(3) solution. Moreover, this (-)-(1R,2S) absolute configuration found by VCD is consistent with the expected stereo-outcome of catalytic hydrogenation of pyruvate into lactate, which supported the (+)-(1S,2R) assignment.

Simultaneous microbatch screening of enantiorecognition on solid chiral selectors using selected mixtures of test-racemates: a case study on cellulose tris(alpha-phenylpropionate) with configurational diversity.

An improved methodology for microbatch screening in the liquid-solid enantioselective adsorption of racemates by solid chiral selector is presented and illustrated by the evaluation of a series of six cellulose tris(alpha-phenylpropionate) presenting a configurational diversity and cellulose tris (4-methylbenzoate). Analyses were performed on 5 mg scale of chiral selector and 150 microL of supernatant containing a mixture of three test-racemates. Fifteen test-racemates were chosen according to their molecular diversity using a hierarchical clustering approach for seven selected three-dimensional molecular properties. The 15 racemates were sorted in five test mixtures composed of three racemates each according to the following constraints: each triplet of test-racemates can be analyzed without peak overlap on a commercially available chiral stationary phase (CSP). The designed five groups of three racemates may be used for the evaluation of other chiral selectors in view of the preparation of CSPs. This methodology improves the throughput of the evaluation and could be automated.

Enantioselective correlation between retention factor and lipophilicity index in chiral separation on cellulose and amylose tris(3,5-dimethylphenylcarbamate) CSPs in reversed mode: A case study.

For a series of alkyl substituted N-arylthiazoline-2-(thi)one atropisomers 1-14, lipophilicity indexes log kw obtained by polycratic RP-HPLC were compared to ln k(+)-S and ln k(-)-R obtained on CHIRALCEL OD-R(R) (reversed mode) and CHIRALPAK AD-RH(R) (reversed mode). Linear correlations were obtained in most cases. It appears that the correlation lines for R and S enantiomers may be parallel, convergent, or divergent, accounting for the observed alpha variation in going from methyl to tert-butyl series. Some tentative hypothesis are given as future investigation routes. Copyright 2000 Wiley-Liss, Inc.

Resolution of some 4-benzofurazanyl and 4-benzofuroxanyl 1, 4-dihydropyridine derivatives by chiral HPLC on whelk-o1 and some polysaccharide chiral stationary phases

The chromatographic chiral resolution of racemic methyl 1, 4-dihydro-2,6-dimethyl-5-nitro-4-benzofurazanyl-3-carboxylates 1 and 2 and their benzofuroxanyl analogues 3 and 4 were studied on Whelk-O1, Chiralcel OD-H, Chiralcel OJ, and Chiralpak AD and AS. These CSPs were selected on the basis of the results of structural searches in Chirbase. Examination of the data and cluster analysis pointed out the influence of benzofurazane-benzofuroxane change versus alpha-beta connection change on retention and enantioselectivity, respectively. The major contribution to the retention change arose from the type of heterocycle, whereas the major contribution to the enantioselectivity change came from the mode of connection (alpha or beta) almost irrespective of the nature of the heterocycle. It resulted in a similarity of behaviour between 1 and 2 on one hand and 3 and 4 on the other as far as capacity factors were concerned, and in a similarity of behaviour between 1 and 3 on the one hand and 2 and 4 on the other as far as enantioselectivities were concerned. Chiralpak AS was selected for semipreparative resolution of the enantiomers. The study of several CSPs allowed us to obtain correlations of structure with retention and enantioselectivity as well as the choice of a semipreparative support to provide the quantities for biological tests. Copyright 1999 Wiley-Liss, Inc.