Mountanea Olga G, Batsika Charikleia S, Mantzourani Christiana, Kokotos Christoforos G, Kokotos George
Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Center of Excellence for Drug Design and Discovery, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Molecules. 2025 Jan 13;30(2):286. doi: 10.3390/molecules30020286.
Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) have emerged as extraordinary bioactive lipids, exhibiting diverse bioactivities, from the enhancement of insulin secretion and the optimization of blood glucose absorption to anti-inflammatory effects. The intricate nature of FAHFAs' structure reflects a synthetic challenge that requires the strategic introduction of ester bonds along the hydroxy fatty acid chain. Our research seeks to create an effective methodology for generating varied FAHFA derivatives. Our primary approach centers on a photochemical hydroacylation reaction, merging terminal alkenes, either -alkenoic acids or -alkenyl alcohols, with commercially available aldehydes. This transformative, environmentally friendly process, orchestrated by phenylglyoxylic acid as the photoinitiator, serves as the linchpin in establishing a practical and relatively simple method for constructing a library of racemic FAHFAs. The ketones produced by the photochemical reactions are easily converted to hydroxy derivatives, which are coupled with caproic, palmitic, or oleic acid, providing a large set of FAHFAs, which broaden our ability for future structure-activity relationship studies.
羟基脂肪酸的脂肪酸酯（FAHFAs）已成为一类特殊的生物活性脂质，具有多种生物活性，从增强胰岛素分泌、优化血糖吸收到抗炎作用。FAHFAs结构的复杂性反映了一个合成挑战，即需要沿着羟基脂肪酸链战略性地引入酯键。我们的研究旨在创建一种有效的方法来生成各种FAHFA衍生物。我们的主要方法集中在光化学氢酰化反应上，将末端烯烃（即ω-烯酸或ω-烯基醇）与市售醛类合并。这个由苯基乙醛酸作为光引发剂精心安排的变革性、环境友好的过程，是建立一个实用且相对简单的构建外消旋FAHFAs库方法的关键。光化学反应产生的酮类很容易转化为羟基衍生物，这些衍生物与己酸、棕榈酸或油酸偶联，提供了大量的FAHFAs，拓宽了我们未来进行构效关系研究的能力。
