Synthetic studies on oligosaccharide probes designed based on the structural motifs in natural products

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05858
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Takahashi Shunya 国立研究開発法人理化学研究所, 環境資源科学研究センター, 特別嘱託研究員 (00202151)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖鎖プローブ / O-抗原多糖 / Ugi反応 / 細胞分化制御 / エステル配糖体

Outline of Final Research Achievements

For elucidation of biological functions, a couple of natural products were selected as target models for designing oligosaccharide probes, and their synthetic studies were carried out. The lipopolysaccharide O-antigen of Pandoraea pulmonicola consists of the trisaccharide repeating unit containing a novel N-oxoprolinyl-kanosamine derivative. However, the absolute configuration of the prolinyl unit regarding the pathogenicity was unknown. In order to determine the absolute configuration, we developed a novel method for preparation of the kanosamine derivative using Ugi reaction. Clostrienose is a fatty-acid glycosyl ester consisting of an unsaturated carboxylic acid and D-galactosyl-L-rhamonose, and regulates cellular differentiation of Clostridium acetobutylicum. Total synthesis of the unstable polyketide was achieved using Migita-Kosugi-Stille coupling as a key step. The undefined structure of the biosynthetic precursor was also unambiguously established by this synthetic work.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

病原菌 P. pulmonicola の O-抗原多糖の合成研究を通じて、特異なアシル基を持つアミノ糖を含む糖鎖プローブの新しい合成法が開発できた。また、嫌気性菌C.acetobutylicumの細胞分化を制御するclostrienoseの全合成を達成し、不安定な官能基を持った糖鎖プローブの創製も可能となるような合成手法を確立することができた。これらの研究成果は、有機合成化学的にも意義のあるものと考えられ、有用な物質生産に関わる合成化学への貢献のみならず、生物化学的にも重要な糖鎖分子をターゲットにしている点から、医療・生化学分野への展開も期待できる