Enantiomeric Separation of Triacylglycerols Consisting of Three Different Fatty Acyls and Their Chiral Chromatographic Elution Behavior.

Chromatographic separation of triacylglycerol (TG) enantiomers is a highly challenging task of analytical chemistry because of the similar physicochemical properties. The analysis of chiral TGs is crucial for improving the knowledge of lipid biochemistry and for understanding the nutritional properties of fats and oils. Thus, this study aimed to systematically investigate the chiral resolution of TGs consisting of three different fatty acyls (FAs). Thirty-three asymmetric TG enantiopairs, including 49 synthesized enantiopure TGs and racemic TGs, were analyzed with a recycling chiral HPLC system. Twenty-six enantiopairs were successfully separated. Overall, having both unsaturated and saturated FAs in the outer positions or a difference in carbon chain length between two saturated FAs at the outer positions favored the separation of enantiomers. The retention time at separation correlated negatively with the sn-3 carbon number of the early eluting enantiomer and positively with the carbon number difference between sn-1 and sn-3. When the samples were studied in separate groups based on unsaturation and regioisomers, both the acyl carbon number and the degree of unsaturation of FAs in all three positions influenced the separation and elution behavior of chiral TGs, indicating an active role of both intermolecular interactions and steric hindrances. This is the first systematic study of the chiral separation of TGs consisting of three different FAs using a large number of enantiopairs. The novel findings on the behavior of TG enantiomers in a chiral environment provide important guidance and reference for a stereospecific study of the chemistry and biochemistry of natural lipids.

Chemoenzymatic Synthesis of ABC-Type Enantiostructured Triacylglycerols by the Use of the p-Methoxybenzyl Protective Group.

This report demonstrates the first asymmetric synthesis of enantiopure structured triacylglycerols (TAGs) of the ABC type presenting three non-identical fatty acids, two of which are unsaturated. The unsaturated fatty acids included monounsaturated oleic acid (C18:1 n-9) and polyunsaturated linoleic acid (C18:2 n-6). This was accomplished by a six-step chemoenzymatic approach starting from (R)- and (S)-solketals. The highly regioselective immobilized Candida antarctica lipase (CAL-B) played a crucial role in the regiocontrol of the synthesis. The synthesis also benefited from the use of the p-methoxybenzyl (PMB) ether protective group, which enabled the incorporation of two different unsaturated fatty acids into the glycerol skeleton. The total of six such TAGs were prepared, four constituting the unsaturated fatty acids in the sn-1 and sn-2 positions, with a saturated fatty acid in the remaining sn-3 position of the glycerol backbone. In the two remaining TAGs, the different unsaturated fatty acids accommodated the sn-1 and sn-3 end positions, with the saturated fatty acid present in the sn-2 position. Enantiopure TAGs are urgently demanded as standards for the enantiospecific analysis of intact TAGs in fats and oils.

Asymmetric Synthesis of Methoxylated Ether Lipids: A Glyceryl Glycidyl Ether Key Building Block Design, Preparation, and Synthetic Application.

The report describes the preparation and use of a double-C3 building block intended as a head group synthon in the synthesis of saturated, mono-, and polyunsaturated 1-O-alkyl-sn-glycerol type methoxylated ether lipids (MELs). The resulting head piece, an enantiopure isopropylidene-protected glyceryl glycidyl ether diastereomer, was accomplished in 49% yield (max 50%) from a 1:1 diastereomeric mixture obtained from R-solketal and racemic epichlorohydrin after treatment with the Jacobsen (S,S)-Co(III)salen catalyst for the hydrolytic kinetic resolution of terminal epoxides. The diol hydrolytic product obtained in 47% yield from the unwanted diastereomer was reconverted into epoxide with an inversion of configuration in a three-step operation involving a highly regioselective lipase. This enabled the recovery of a substantial amount of diastereopure material after a subsequent treatment with the Jacobsen catalyst to furnish the oxirane head piece in altogether 72% yield of higher than 99% diastereomeric purity. A modified synthesis of a monounsaturated 16:1 MEL confirmed the correct stereochemistry and excellent enantiopurity of the head piece and resulted in a dramatic improvement in yields, efficiency, and economy of the synthesis.