4-Methyltetrahydropyran as a Convenient Alternative Solvent for Olefin Metathesis Reaction: Model Studies and Medicinal Chemistry Applications

  • ACS Sustain Chem Eng. 2020 Dec 14;8(49):18215-18223. doi: 10.1021/acssuschemeng.0c06668.
Tomasz Nienałtowski  1  2 ,  Paweł Krzesiński  1 ,  Marcel E Baumert  1 ,  Aleksandra Skoczeń  1 ,  Ewa Suska-Kauf  1 ,  Jolanta Pawłowska  2 ,  Anna Kajetanowicz  1 ,  Karol Grela  1
Affiliations
  • 1. Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland.
  • 2. Pharmaceutical Works Polpharma SA, Pelplińska 19, 83-200 Starogard Gdański, Poland.
PMID: 33344098 DOI: 10.1021/acssuschemeng.0c06668
Abstract

A number of metathesis reactions were successfully conducted in 4-methyltetrahydropyran, including both standard model dienes, as well as more complex substrates, such as analogues of biologically active compounds and active pharmaceutical ingredients. To place this solvent in a context of pharmaceutical R + D, larger-scale syntheses of SUAM 1221, a prolyl endopeptidase inhibitor with potential application in Alzheimer disease treatment, and a derivative of sildenafil, an analogue of the popular Viagra drug, were executed. In the latter case, despite all the setup being made in air, the metathesis reaction at a 33 g scale proceeded very well with relatively low catalyst loading and without need of aqueous workup or column chromatography.

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