Bo Lamm

Doubly tethered tertiary amide selectors: Modified version of Doyle et al.'s naproxen chiral stationary phase

Abstract The synthesis of an ( S )-naproxen-derived chiral stationary phase (CSP) that differs from those of Doyle et al . [T.D. Doyle, C.A. Brunner and E. Smith, US Pat. , 4919 803 (1990) and T.D. Doyle, in W.J. Lough (Editor), Chiral Liquid Chromatography, Chapman & Hall, New York, 1989, pp. 102-128] and of Oliveros et al . [L. Oliveros, C. Minguillon, B. Desmazieres and P. Desbene, J. Chromatogr., 589 (1992) 53 and 606 (1992) 9] is reported. Instead of linking naproxen to a primary amino group in the tether, linkage is to a secondary amino group. This avoids the presence of an amide hydrogen which often serves to increase retention, attenuate enantioselectivity and diminish the efficiency of the CSP. The presently described CSP 2 typically shows improved performance relative to those described by the Doyle et al . and Oliveros et al .

Synthesis of the enantiomers of felodipine and determination of their absolute configuration

Abstract The pure enantiomers of felodipine, 1 , have been synthesized by chromatographic separation of diastereomeric esters with (R)-1-(p-toluenesulfonyl)-3-trityloxypropan-2-ol, 3 , as an easily removable chiral auxiliary. Absolute configurations have been deduced via X-ray crystallography on a (R)-mandelic acid ester, 9B .

Enantiomer separation of tocainide and some of its analogues and derivatives on a Chirasil-Val capillary column☆

Abstract The enantiomeric separation of tocainide [R,S-2-amino-N-(2,6-xylyl)propanoic acid amide] and related compounds has been studied on a Chirasil-Val capillary column. As heptafluorobutyramide derivatives the separation improves with increasing bulkiness of the alkyl substituent at the chiral carbon. If one of the amide groups is alkylated the separation deteriorates. When tocainide is derivatized with different reagents acyl groups show better separation than acyloxy ones. Bulky groups are also advantageous. In this chromatographic system tocainide hydantoin, obtained from a tocainide conjugate by the action of alkali, is only partly separated into its enantiomers. Better separation can be obtained on a packed column with an ester phase after extractive alkylation with a new chiral alkylating agent myrtenyl bromide. The drawback is that the hydantoin partly racemizes under the alkaline conditions used.

Degradation of perfluoroacyl derivatives of tocainide and some of its analogues in the presence of an excess of anhydride reagent

Abstract The perfluoroacylation of tocainide has been studied. The initially formed perfluoroacylamides were found to be degraded by an excess of perfluoroacyl anhydride. The reaction of tocainide with heptafluorobutyric anhydride gave similar results in six different solvents. Comparable amounts of decomposition occurred with trifluoroacetyl and pentafluoropropionyl anhydrides as reagents. Six new products were separated by gas chromatography and their structures tentatively assigned based on comparison with a deuterated analogue and mass spectral analysis including high resolution measurements: dehydrated and dehydrogenated heptafluorobutyryl (HFB)-tocainide, “apparent” pyruvic xylidide which still retains the perfluoro group, dehydrated HFB-tocainide and dehydrogenated HFB-tocainide. In the presence of water, these compounds could be quantitatively converted into HFB-tocainide with loss of tocainides chirality. Studies with some tocainide analogues having a primary amino group and a secondary amide demonstrated that these functional groups are required to give labile HFB derivatives. On the contrary, stable derivatives of tocainide were formed with heptafluorobutyryl chloride and N-methyl-bis(heptafluorobutyramide).