Jónsdóttir Lena Rós, Haraldsson Gudmundur G
Science Institute, Chemistry Department, University of Iceland, Dunhaga 3, 107 Reykjavik, Iceland.
Molecules. 2024 Dec 5;29(23):5745. doi: 10.3390/molecules29235745.
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 -1 or -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 -2 position. This was accomplished by a six-step chemoenzymatic approach starting from enantiopure ()- and ()-solketals. The highly regioselective immobilized 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.
本报告描述了对映体纯结构三酰甘油（TAGs）聚焦文库的不对称合成，该文库由单一饱和脂肪酸（C6、C8、C10、C12、C14或C16）、纯生物活性n-3多不饱和脂肪酸（EPA或DHA）和一种强效药物（布洛芬或萘普生）组成，旨在作为一种新型前药。甘油主链的一个末端-1或-3位被饱和脂肪酸占据，另一个被多不饱和脂肪酸占据，药物实体存在于-2位。这是通过从对映体纯的（）-和（）-缩酮开始的六步化学酶法实现的。高度区域选择性的固定化脂肪酶（CAL-B）在合成的区域控制中起关键作用。总共制备、分离并充分表征了所有组合，即48种此类前药TAGs，以及60种酰基甘油中间体，产率非常高至优异。
