Efficient synthesis of diethyl, dialkyl α-hydroxy-propylenebisphosphonates and related 5-phosphonoyl-1,2-oxaphospholane 2-oxides

A series of new dialkyl α-diethylphosphonoylethyl-α-hydroxy-ethylphosphonates were prepared using the Pudovik reaction of the corresponding γ-oxophosphonate with dialkyl phosphites performed on the surface of Al₂O₃/KF. The adducts revealed unexpected reactivity in the attempted O-acylation reaction, and provided the corresponding 5-phosphonoyl-1,2-oxaphospholane 2-oxides. On treatment with Cs₂CO₃, instead of the expected rearrangement a cyclization reaction leading to the same ring products took place. Three of the phosphonoylethyl-α hydroxy-ethylphosphonates, along with two phosphonoylmethyl analogues revealed significant and selective anticancer effect on A431 cells, and occasionally, on PC-3 and MDA-MB 231 cells.

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