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

A novel one-pot method for the preparation of N-substituted 2-phopshorylpyrrolidines from readily available 4,4-diethoxybutan-l-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. (C) 2020 Elsevier Ltd. All rights reserved.