Synthesis of Enantiostructured Triacylglycerol Prodrugs Constituting an Active Drug Located at Terminal <i>sn</i>-1 and <i>sn</i>-3 Positions of the Glycerol Backbone
The current paper reports the asymmetric synthesis of a focused library of enantiostructured triacylglycerols (TAGs) constituting a potent drug of the NSAID type (ibuprofen or naproxen) along with a pure bioactive n-3 polyunsaturated fatty acid (PUFA) intended as a novel type of prodrug. In this sec...
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2025-02-01
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| author | Lena Rós Jónsdottir Gudmundur G. Haraldsson |
| author_facet | Lena Rós Jónsdottir Gudmundur G. Haraldsson |
| author_sort | Lena Rós Jónsdottir |
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| description | The current paper reports the asymmetric synthesis of a focused library of enantiostructured triacylglycerols (TAGs) constituting a potent drug of the NSAID type (ibuprofen or naproxen) along with a pure bioactive n-3 polyunsaturated fatty acid (PUFA) intended as a novel type of prodrug. In this second category, a TAG prodrug of the terminal <i>sn</i>-1 or <i>sn</i>-3 position of the glycerol skeleton is acylated with a single saturated medium-chain fatty acid (C6, C8, C10, or C12), and another with the drug entity; the PUFA (EPA or DHA) is located in the <i>sn</i>-2 position. This was accomplished by a six-step chemoenzymatic approach, two of which were promoted by a lipase, 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. The most challenging key step involved the incorporation of the drugs that were activated as oxime esters by the lipase exclusively in the terminal position of glycerol that is protected as a benzyl ether. All combinations, a total of 32 such prodrug TAGs, were prepared, isolated, and fully characterized, along with 24 acylglycerol intermediates, obtained in very-high-to-excellent yields in the majority of cases. |
| format | Article |
| id | doaj-art-77f8a3c0400a4bf79b374d7fad931d7e |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Molecules |
| spelling | doaj-art-77f8a3c0400a4bf79b374d7fad931d7e2025-08-20T02:05:19ZengMDPI AGMolecules1420-30492025-02-0130599110.3390/molecules30050991Synthesis of Enantiostructured Triacylglycerol Prodrugs Constituting an Active Drug Located at Terminal <i>sn</i>-1 and <i>sn</i>-3 Positions of the Glycerol BackboneLena Rós Jónsdottir0Gudmundur G. Haraldsson1Science Institute, Chemistry Department, University of Iceland, Dunhaga 3, 107 Reykjavik, IcelandScience Institute, Chemistry Department, University of Iceland, Dunhaga 3, 107 Reykjavik, IcelandThe current paper reports the asymmetric synthesis of a focused library of enantiostructured triacylglycerols (TAGs) constituting a potent drug of the NSAID type (ibuprofen or naproxen) along with a pure bioactive n-3 polyunsaturated fatty acid (PUFA) intended as a novel type of prodrug. In this second category, a TAG prodrug of the terminal <i>sn</i>-1 or <i>sn</i>-3 position of the glycerol skeleton is acylated with a single saturated medium-chain fatty acid (C6, C8, C10, or C12), and another with the drug entity; the PUFA (EPA or DHA) is located in the <i>sn</i>-2 position. This was accomplished by a six-step chemoenzymatic approach, two of which were promoted by a lipase, 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. The most challenging key step involved the incorporation of the drugs that were activated as oxime esters by the lipase exclusively in the terminal position of glycerol that is protected as a benzyl ether. All combinations, a total of 32 such prodrug TAGs, were prepared, isolated, and fully characterized, along with 24 acylglycerol intermediates, obtained in very-high-to-excellent yields in the majority of cases.https://www.mdpi.com/1420-3049/30/5/991asymmetric synthesisenantiostructured triacylglycerolslipasen-3 PUFAsacylglycerol prodrugs(<i>S</i>)-ibuprofen |
| spellingShingle | Lena Rós Jónsdottir Gudmundur G. Haraldsson Synthesis of Enantiostructured Triacylglycerol Prodrugs Constituting an Active Drug Located at Terminal <i>sn</i>-1 and <i>sn</i>-3 Positions of the Glycerol Backbone Molecules asymmetric synthesis enantiostructured triacylglycerols lipase n-3 PUFAs acylglycerol prodrugs (<i>S</i>)-ibuprofen |
| title | Synthesis of Enantiostructured Triacylglycerol Prodrugs Constituting an Active Drug Located at Terminal <i>sn</i>-1 and <i>sn</i>-3 Positions of the Glycerol Backbone |
| title_full | Synthesis of Enantiostructured Triacylglycerol Prodrugs Constituting an Active Drug Located at Terminal <i>sn</i>-1 and <i>sn</i>-3 Positions of the Glycerol Backbone |
| title_fullStr | Synthesis of Enantiostructured Triacylglycerol Prodrugs Constituting an Active Drug Located at Terminal <i>sn</i>-1 and <i>sn</i>-3 Positions of the Glycerol Backbone |
| title_full_unstemmed | Synthesis of Enantiostructured Triacylglycerol Prodrugs Constituting an Active Drug Located at Terminal <i>sn</i>-1 and <i>sn</i>-3 Positions of the Glycerol Backbone |
| title_short | Synthesis of Enantiostructured Triacylglycerol Prodrugs Constituting an Active Drug Located at Terminal <i>sn</i>-1 and <i>sn</i>-3 Positions of the Glycerol Backbone |
| title_sort | synthesis of enantiostructured triacylglycerol prodrugs constituting an active drug located at terminal i sn i 1 and i sn i 3 positions of the glycerol backbone |
| topic | asymmetric synthesis enantiostructured triacylglycerols lipase n-3 PUFAs acylglycerol prodrugs (<i>S</i>)-ibuprofen |
| url | https://www.mdpi.com/1420-3049/30/5/991 |
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