One-pot imination / Arbuzov reaction of 4-aminobutanal derivatives: Synthesis of 2-phosphorylpyrrolidines and evaluation of anticancer activity

• Published in: Tetrahedron Vol. 76; no. 33; pp. 131369 - 131374
• Main Authors: Smolobochkin, Andrey V., Turmanov, Rakhymzhan A., Gazizov, Almir S., Voloshina, Alexandra D., Voronina, Julia K., Sapunova, Anastasiia S., Burilov, Alexander R., Pudovik, Michail A.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 14.08.2020; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Cytotoxicity; Nitrogen heterocycles; Phosphorylation; Physical Sciences; Science & Technology; Sulfonylamides; Ureas; Ureas; Cytotoxicity; Phosphorylation; Sulfonylamides; Nitrogen heterocycles; ASYMMETRIC-SYNTHESIS; PHOSPHONATES; ACIDS; ESTERS; INHIBITORS; CYCLIZATION
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2020.131369

A novel one-pot method for the preparation of N-substituted 2-phopshorylpyrrolidines from readily available 4,4-diethoxybutan-1-amine derivatives and P (III) acid chlorides is described. The presented method benefits from simple reaction and work-up procedures, mild reaction conditions, avoids protecting group introduction-removal stages and provides a straightforward access to target compounds. In vitro cytotoxicity studies indicate that obtained 2-phopshorylpyrrolidines inhibit selectively M-Hela tumor cells growth. The activity of some derivatives towards M-Hela and MCF-7 tumor cells is comparable to that of reference drug Tamoxifen. In contrast to Tamoxifen and Doxorubicin tested compounds have no cytotoxic effects on normal cells. [Display omitted] •A novel method of synthesis of N-substituted 2-phopshorylpyrrolidines is developed.•Some of obtained 2-phopshorylpyrrolidines inhibit M-Hela and MCF-7 tumor cells growth.•In contrast to Tamoxifen and Doxorubicin tested compounds do not affect normal cells.