A New Family of Rigid Dienone Musks Challenges the Perceptive Range of the Human Olfactory Receptor OR5AN1
A New Family of Rigid Dienone Musks Challenges the Perceptive Range of the Human Olfactory Receptor OR5AN1
复制标题
新型刚性二烯酮麝香家族挑战人类嗅觉受体 OR5AN1 的感知范围
作者：
Quanrui Wang;Sereina Riniker;P. Kraft;Jie Liu;V. Hürlimann;R. Emter;A. Natsch;C. Esposito;Stephanie M. Linker;Y. Zou;Lijun Zhou
摘要通过不同醛与丁-3-烯-1-炔-1-基锂的烷基化反应，以及随后的Saucy-Marbet转移乙烯化-Claisen重排和分子内Diels-Alder反应的多米诺反应，最后通过刘易斯酸催化双键异构化，发现了一类新的二烯酮麝香。新合成的二烯酮结构具有令人愉快的麝香气味，显示脂肪，轻微的水果和绿色方面。尽管基于QM/MM计算，通过计算机模拟预测二烯酮麝香与OR 5AN 1受体结合，但发现它们在体外测定中无活性。后者的结果表明，OR 5AN 1受体不是主要的麝香受体，但主要负责某些大环酮和硝基麝香的动物性。
Abstract A new family of dienone musks was discovered by alkylation of different aldehydes with but-3-en-1-yn-1-yllithium and subsequent domino reaction of a Saucy–Marbet transfer vinylation–Claisen rearrangement with an intramolecular Diels–Alder reaction, and concluding Lewis acid catalyzed double-bond isomerization. The newly synthesized dienone structures possess pleasant musk odors displaying fatty, slightly fruity and green facets. Although the dienone musks were predicted in silico to bind to the OR5AN1 receptor based on QM/MM calculations, they were found to be inactive in the in vitro assay. The latter results suggest that the OR5AN1 receptor is not the prime musk receptor but primarily responsible for the animalic character of certain macrocyclic ketones and nitro musks.