Efficient Synthesis of Diethyl, Dialkyl α-Hydroxy-propylene-bisphosphonates and Related 5-Phosphonoyl-1,2-oxaphospholane 2-Oxides

A series of new dialkyl alfa-diethylphosphonoylethyl-alfa-hydroxy-ethylphosphonates were prepared using the Pudovik reaction of the corresponding gamma-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-alfa-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.