SYNTHESIS OF SUBSTITUTED t-BUTYL 3-ALKYLOXINDOLE-3-CARBOXYLATES FROM DI-t-BUTYL (2-NITROPHENYL)MALONATES

Using a novel tandem reduction-cyclization, we synthesized t-butyl 3-alkyloxindole-3-carboxylates from the di-t-butyl 2-alkyl-2-(2-nitrophenyl)malonate. Introduction of an α-substituent to the di-t-butyl 2-(2-nitrophenyl)-malonates and addition of acid promoted reactivity. This methodology was successfully applied to gram-scale-synthesis of the t-butyl 3-methyloxindole-3-carboxylate 1 and 3-hydroxymethyl-3-methyloxindole 2 without silica gel column chromatography.Part of this work was supported by the Kansai University Subsidy for Supporting Young Scholars, 2015 “Development of macrocyclization reaction via a photoaffinity reaction”, JSPS KAKENHI Grant Number 15K18903, Grant-in-Aid for Young Scientists (B) – Japan and MEXT – Supported Program for the Strategic Research Foundation at Private Universities (2013–2017) – Japan.2015年度関西大学若手研究者育成経

BUILDING AN INTERNATIONAL NETWORK EXCHANGE PROGRAM OF EDUCATION AND RESEARCH FOR GRADUATE COURSE STUDENTS IN LIFE SCIENCE AND BIOTECHNOLOGY

We proposed an "International Network Exchange Program of Education and Research for Graduate Course Students in Life Science and Biotechnology" to the Kansai University Special Research Fund 2007 in order to promote international student exchange in the Graduate School of Engineering. In this program, we have successfully sent 8 graduate students to study for about a month in Malaysia, Thailand, Indonesia, and Germany. We hope the result of our efforts will promote an acceleration of international student exchange in the Graduate School of Engineering.LIFE SCIENCE AND BIOTECHNOLOGY, 50th anniversary editio

A Potent Inhibitor of SIK2, 3, 3′, 7-Trihydroxy-4′-Methoxyflavon (4′-O-Methylfisetin), Promotes Melanogenesis in B16F10 Melanoma Cells

Flavonoids, which are plant polyphenols, are now widely used in supplements and cosmetics. Here, we report that 4′-methylflavonoids are potent inducers of melanogenesis in B16F10 melanoma cells and in mice. We recently identified salt inducible kinase 2 (SIK2) as an inhibitor of melanogenesis via the suppression of the cAMP-response element binding protein (CREB)-specific coactivator 1 (TORC1). Using an in vitro kinase assay targeting SIK2, we identified fisetin as a candidate inhibitor, possibly being capable of promoting melanogenesis. However, fisetin neither inhibited the CREB-inhibitory activity of SIK2 nor promoted melanogenesis in B16F10 melanoma cells. Conversely, mono-methyl-flavonoids, such as diosmetin (4′-O-metlylluteolin), efficiently inhibited SIK2 and promoted melanogenesis in this cell line. The cAMP-CREB system is impaired in Ay/a mice and these mice have yellow hair as a result of pheomelanogenesis, while Sik2+/−; Ay/a mice also have yellow hair, but activate eumelanogenesis when they are exposed to CREB stimulators. Feeding Sik2+/−; Ay/a mice with diets supplemented with fisetin resulted in their hair color changing to brown, and metabolite analysis suggested the presence of mono-methylfisetin in their feces. Thus, we decided to synthesize 4′-O-methylfisetin (4′MF) and found that 4′MF strongly induced melanogenesis in B16F10 melanoma cells, which was accompanied by the nuclear translocation of TORC1, and the 4′-O-methylfisetin-induced melanogenic programs were inhibited by the overexpression of dominant negative TORC1. In conclusion, compounds that modulate SIK2 cascades are helpful to regulate melanogenesis via TORC1 without affecting cAMP levels, and the combined analysis of Sik2+/− mice and metabolites from these mice is an effective strategy to identify beneficial compounds to regulate CREB activity in vivo

環境アポトジェンを含む環境汚染化学物質の作用動態解析と化学生態学的防除法の開発研究プロジェクト

プロジェクト研究報告概要集　　戦略的研究基盤形成支援事業プロジェクト　研究代表者:土戸哲明　研究担当者:池内俊彦・下家浩二・上里新一・吉田宗弘・福永健治・安原裕紀・長谷川喜衛・岩木宏明・老川典夫・松村吉

A synthesis of (.+-.)-yohimbine

This article does not have an abstract