Syntheses and structure-activity relationship studies of diaryl ether type PTP 1B inhibitors

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07720
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Prefectural University of Hiroshima
• Principal Investigator: Noshita Toshiro 県立広島大学, 生命環境学部, 教授 (50285574)
• Co-Investigator(Kenkyū-buntansha): 田井 章博 県立広島大学, 生命環境学部, 教授 (70284081)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 天然物合成 / 生物活性物質 / 有機合成化学 / 2型糖尿病 / プロテインチロシンホスファターゼ1B阻害剤

Outline of Final Research Achievements

With the aim of developing new therapeutic agents for type 2 diabetes, the first objective was to synthesize the diarylether compound having protein tyrosine phosphatase 1B (PTP1B) inhibitory activity, which was isolated from Acanthopanax senticosus and structurally determined by Li et al. And we established the synthesis method. However, There were found that the analytical data and bioactivity of the compound obtained by the synthesis did not at all coincide with the data in the isolation report by Li et al. Therefore, all structural isomers that can be considered rationally were also synthesized, comparison of various in analytical data, and detailed examination of spectra in the isolated literature were conducted. As a result, the diaryl ether type compound described in the isolation report by Li et al. did not exist.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

Liらによってエゾウコギ（Acanthopanax senticosus）に含まれる強いPTP1B阻害物質として報告されたジアリールエーテル化合物およびその異性体の合成法を確立できたことから、この型の化合物の合成法としては古典的なウルマンエーテル合成が適していることが判明した。
一方、合成で得た化合物の各種機器分析データとLiらによる天然物のデータは一致せず、また合成した化合物は全くPTP1B阻害活性を示さなかった。Liらのデータを仔細に検討したところ、本研究で目的とした化合物は天然には存在せず、本化合物に糖尿病治療薬の可能性がないことがわかった。