2. Academic Validation
  3. Unified synthesis and assessment of tumor cell migration inhibitory activity of optically active UTKO1, originally designed moverastin analog

Unified synthesis and assessment of tumor cell migration inhibitory activity of optically active UTKO1, originally designed moverastin analog

  • Biosci Biotechnol Biochem. 2021 Jan 7;85(1):160-167. doi: 10.1093/bbb/zbaa062.
Yusuke Ogura 1,  Hiroki Kobayashi 2,  Masaya Imoto 2,  Hidenori Watanabe 1,  Hirosato Takikawa 1
Affiliations

Affiliations

  • 1 Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan.
  • 2 Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University , Hiyoshi, Kohoku-ku, Yokohama, Japan.
PMID: 33577660 DOI: 10.1093/bbb/zbaa062
Abstract

UTKO1 is a synthetic analog of a natural tumor cell migration inhibitor, moverastin, isolated from microbial extracts of Aspergillus sp. 7720. UTKO1 was initially developed as a mixture of the stereoisomers. In this study, a concise and unified synthesis of the 4 optically active stereoisomers of UTKO1 was achieved from a known optically pure dihydro-α-ionone through a 5-step sequence. The key transformation in the synthesis was a Nozaki-Hiyama-Kishi (NHK) reaction between an optically active enoltriflate and a known aldehyde to install the chiral allylic hydroxy group at C2'. Simple chromatographic separation of the 2 diastereomers with regard to the allylic hydroxy group was possible by the derivatization into the corresponding acetals with Nemoto's optical resolution reagent, (S)- or (R)-5-allyl-2-oxabicyclo[3.3.0]octene (ALBO). All 4 synthetic stereoisomers of UTKO1 exhibited comparable tumor cell migration inhibitory activity.

Keywords

NHK reaction; UTKO1; cell migration; moverastin.

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