Total synthesis of (±)-spirotenuipesine A, a promoter of neurotrophic factor secretion from glial cells

• Published in: Tetrahedron letters Vol. 64; pp. 152723 - 152727
• Main Authors: Yanagimoto, Tsuyoshi, Yamada, Sayo, Kasai, Yusuke, Yamamoto, Hirofumi, Kubo, Miwa, Fukuyama, Yoshiyasu, Imagawa, Hiroshi
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 02.02.2021; Elsevier
• Subjects: 1321Nl cells; Chemistry; Chemistry, Organic; Neurite outgrowth; Neurotrophic factor; PC12 cells; Physical Sciences; Science & Technology; Spirotenuipesine; Neurotrophic factor; 1321Nl cells; Spirotenuipesine; Neurite outgrowth; PC12 cells; SPIROTENUIPESINE-A; ALCOHOL; DERIVATIVES
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2020.152723

[Display omitted] •(±)-spirotenuipesine A was synthesized via Ireland-Claisen rearrangement.•The stereochemistry of the newly formed quaternary carbon was fully controlled.•The synthetic sample showed neurotrophic factor secretion-promoting activity. Naturally occurring (+)-spirotenuipesines A and B are known to promote the biosynthesis of neurotrophic factors in glial cells. Therefore, these compounds can be expected to constitute promising drug leads for neurodegenerative diseases such as Alzheimer's disease. In order to obtain sufficient amounts for biological evaluation, (±)-spirotenuipesine A was synthesized via a stereoselective Ireland-Claisen rearrangement as a key step. A culture medium of 1321N1 cells treated with the obtained synthetic racemic compound showed differentiation-inducing activity against PC12 cells, resulting in a morphological change.