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

Abstract 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.