Tsukamoto Shuntaro, Hlokoane Oriel, Miyako Kei, Irie Raku, Sakai Ryuichi, Oikawa Masato
Graduate School of Nanobioscience, Yokohama City University Seto 22-2, Kanazawa-ku Yokohama 236-0027 Japan
Department of Pharmacy, National University of Lesotho P.O. Roma 180 Maseru Lesotho.
RSC Adv. 2022 Aug 10;12(34):22175-22179. doi: 10.1039/d2ra03744k. eCollection 2022 Aug 4.
Herein we report stereoselective generation of two skeletons, 1,3-dioxane and tetrahydropyranol, by oxa-Michael reaction as the key reaction from δ-hydroxyenone. The construction of the 1,3-dioxane skeleton, achieved through hemiacetal formation followed by oxa-Michael reaction from δ-hydroxyenone, was exploited to access structurally diverse heterotricyclic artificial glutamate analogs. On the other hand, formation of a novel tetrahydro-2-pyranol skeleton was accomplished by the inverse reaction order: oxa-Michael reaction followed by hemiacetal formation. Thus, this study succeeded in showing that structural diversity in a compound collection can be acquired by interchanging the order of just two reactions. Among the skeletally diverse, heterotricyclic artificial glutamate analogs synthesized in this study, a neuronally active compound named TKM-50 was discovered in the mice assay.
在此，我们报道了以δ-羟基烯酮为原料，通过氧杂-Michael反应作为关键反应，立体选择性地生成1,3-二氧六环和四氢吡喃醇两种骨架。通过半缩醛形成，随后由δ-羟基烯酮进行氧杂-Michael反应实现的1,3-二氧六环骨架的构建，被用于合成结构多样的杂三环人工谷氨酸类似物。另一方面，新型四氢-2-吡喃醇骨架的形成则通过相反的反应顺序实现：先进行氧杂-Michael反应，然后进行半缩醛形成。因此，本研究成功表明，仅通过交换两个反应的顺序就可以在化合物库中获得结构多样性。在本研究中合成的骨架多样的杂三环人工谷氨酸类似物中，在小鼠实验中发现了一种名为TKM-50的具有神经活性的化合物。
