Synthesis and in vitro antitumour activity of 4(R)-methyl-3-O-phosphonomethyl-α-l-threose nucleosides

Synthesis of Novel 2,2'-Anhydro-L-threosylpyrimidine Phosphonates

“…Protected sugar 5 was converted to 1-O-acetyl-2-O-benzoyl-3-O-phosphonate-L-threose (8) by a previously reported three-step procedure. [21] Then, different bases were introduced by Vorbruggen glycosylation to give the protected phosphonate nucleoside analogues 9a～9c, subsequent debenzoylation of 9a～9c with NH 3 /MeOH produced 10a～10c.…”

“…Scheme 2 Formation of 2,2'-anhydro-L-threonucleoside analogues 10b, 10c, and previously reported 4(R)-methyl analogue 10d. [21] All the reactions furnished the corresponding 2,2'-anhydro-L-threonucleoside phosphonate analogues (Scheme 2). Finally, following the classical procedures for hydrolysis of nucleoside phosphonate, compounds 11a ～ 11d were smoothly hydrolyzed by treatment with TMSBr/lutidine to produce corresponding phosphonic acids 12a～12d without disclosure of 2,2'-anhydro ring (Scheme 3).…”