Synthesis and biological evaluation of 1',2'-seconucleo-5'-phosphonates

A series of 1',2'-seconucleophosphonate analogues were prepared containing adenine, cytosine, thymine, and uracil as the nucleobase. The synthetic methodology is efficient and uses chloromethyl ethers derived from the chirons diethyl (3S)-(benzyloxy)-(2R)-hydroxybutanephosphonate (1) and diethyl (3S),4-bis(benzyloxy)-(2R)-hydroxybutanephosphonate (2). Selected deblocked derivatives, i.e., two monoesters (13 and 14), four phosphonic acids (15-18), and one cyclic phosphonate (23), were screened for in vitro activity against certain RNA, adeno, and HIV viruses. All of them were found to be devoid of activity.