title: One-Pot Evolution of Ageladine A through a Bio-Inspired Cascade towards Selective Modulators of Neuronal Differentiation.
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.
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.|Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka-shi, Osaka, 560-0043, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Otsuka
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.|Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Tsubokura
authors.affiliation: Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, Kazan, 420008, Russia.
authors.forename: Almira
authors.initials: A
authors.lastname: Kurbangalieva
authors.affiliation: Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.|Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Arai
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka-shi, Osaka, 560-0043, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
authors.affiliation: Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.|Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakao
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan. kotzenori@riken.jp.|Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, Kazan, 420008, Russia. kotzenori@riken.jp.|JST, PRESTO, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan. kotzenori@riken.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D032701:Biomimetics / Q000379:methods; D002454:Cell Differentiation; D006146:Guanidines / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000138:chemical synthesis; D013329:Structure-Activity Relationship; D000097603:Dyrk Kinases
chemical_list: D000814:Aniline Compounds; D006146:Guanidines; D007093:Imidazoles; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011758:Pyrroles; D054852:Small Molecule Libraries; D000097603:Dyrk Kinases; C482289:Ageladine A; C014973:2-aminoimidazole
keywords: 2-aminoimidazole; ageladine A; natural products; neural differentiation; one-pot synthesis