Nienałtowski Tomasz, Krzesiński Paweł, Baumert Marcel E, Skoczeń Aleksandra, Suska-Kauf Ewa, Pawłowska Jolanta, Kajetanowicz Anna, Grela Karol
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland.
Pharmaceutical Works Polpharma SA, Pelplińska 19, 83-200 Starogard Gdański, Poland.
ACS Sustain Chem Eng. 2020 Dec 14;8(49):18215-18223. doi: 10.1021/acssuschemeng.0c06668. Epub 2020 Nov 25.
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.
一系列复分解反应在4-甲基四氢吡喃中成功进行，反应底物包括标准模型二烯以及更复杂的底物，如生物活性化合物类似物和活性药物成分。为了将这种溶剂置于药物研发的背景下，开展了更大规模的合成，即合成了具有治疗阿尔茨海默病潜在应用的脯氨酰内肽酶抑制剂SUAM 1221，以及流行的伟哥药物类似物西地那非的衍生物。在后一种情况下，尽管所有操作都是在空气中进行的，但33克规模的复分解反应在相对较低的催化剂用量下进行得非常顺利，无需水相后处理或柱色谱法。
