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

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.

• Authors: Yusuke Ogura, Hiroki Kobayashi, Masaya Imoto, Hidenori Watanabe, Hirosato Takikawa
• Journal: Bioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 85 Issue 1 Pg. 160-167 (Jan 07 2021) ISSN: 1347-6947 [Electronic] England
• PMID: 33577660 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.

Chemical References

• Antineoplastic Agents
• Benzaldehydes
• Cyclohexanones
• UTKO1 compound
• moverastin A

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Benzaldehydes (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Chemistry Techniques, Synthetic
• Cyclohexanones (chemistry)
• Drug Design
• Humans