Synthesis of Enantiostructured Triacylglycerols Possessing a Saturated Fatty Acid, a Polyunsaturated Fatty Acid and an Active Drug Intended as Novel Prodrugs

This report describes the asymmetric synthesis of a focused library of enantiopure structured triacylglycerols (TAGs) comprised of a single saturated fatty acid (C6, C8, C10, C12, C14 or C16), a pure bioactive n-3 polyunsaturated fatty acid (EPA or DHA) and a potent drug (ibuprofen or naproxen) inte...

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Bibliographic Details
Main Authors: Lena Rós Jónsdóttir, Gudmundur G. Haraldsson
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/29/23/5745
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Summary:This report describes the asymmetric synthesis of a focused library of enantiopure structured triacylglycerols (TAGs) comprised of a single saturated fatty acid (C6, C8, C10, C12, C14 or C16), a pure bioactive n-3 polyunsaturated fatty acid (EPA or DHA) and a potent drug (ibuprofen or naproxen) intended as a novel type of prodrug. One of the terminal <i>sn</i>-1 or <i>sn</i>-3 positions of the glycerol backbone is occupied with a saturated fatty, the remaining one with a PUFA, and the drug entity is present in the <i>sn</i>-2 position. This was accomplished by a six-step chemoenzymatic approach starting from enantiopure (<i>R</i>)- and (<i>S</i>)-solketals. The highly regioselective immobilized <i>Candida antarctica</i> lipase (CAL-B) played a crucial role in the regiocontrol of the synthesis. All combinations, a total of 48 such prodrug TAGs, were prepared, isolated and fully characterized, along with 60 acylglycerol intermediates, obtained in very high to excellent yields.
ISSN:1420-3049