One‐Pot Evolution of Ageladine A through a Bio‐Inspired Cascade towards Selective Modulators of Neuronal Differentiation. Issue 41 (25th August 2016)

• Record Type: Journal Article
• Authors: Iwata, Takayuki; Otsuka, Satoshi; Tsubokura, Kazuki; Kurbangalieva, Almira; Arai, Daisuke; Fukase, Koichi; Nakao, Yoichi; Tanaka, Katsunori
• Is Part Of: Chemistry. Volume 22:Issue 41(2016)
• Page Start: 14707
• Page End: 14716
• Publication Date: 2016-08-25
• Subjects: ageladine A -- 2-aminoimidazole -- natural products -- neural differentiation -- one-pot synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201602651
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A bio‐inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1‐substituted derivatives. This cascade features a 2‐aminoimidazole formation that is modeled after an arginine post‐translational modification and an aza‐electrocyclization. It can be effectively carried out in a one‐pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible. We found that some compounds out of this structurally novel library show a significant activity in modulating the neural differentiation. Namely, these compounds selectively activate or inhibit the differentiation of neural stem cells to neurons, while being negligible in the differentiation to astrocytes. This study represents a successful case in which the native biofunction of a natural product could be altered by structural modifications. Abstract : One‐pot wonder ! A bio‐inspired one‐pot cascade reaction, which features a 2‐aminoimidazole formation with subsequent aza‐electrocyclization for the construction of the marine natural product ageladine A and its derivatives, has been developed. Some of these derivatives selectively activated or inhibited the differentiation of neural stem cells to neurons. Ageladine A was thus transformed into a new selective neural‐differentiation modulator.