Bismethylene triphosphate

Scheme 51 Synthesis of bismethylene triphosphate analogue 259 of nucleosides...

Synthesis of the modified triphosphate subunit was accomplished starting from ethyl bis(bromomethyl)phosphinate 253 (Scheme 51). An Arbusov reaction with triethyl phosphite and trimethyl phosphite, respectively, produced bis (phosphonomethyl)phosphjnate 255 in 40% overall yield. A selective monodemethylation by cyanide and acidificaticHi led to monophosphonic acid 256. Bismethylene triphosphate (BMT) 258 analogues of nucleosides were obtained by coupling of the 5 -free OH nucleosides 257 with phosphonate 256 under Mitsunobu conditions [181,182]. TMSBr mediated deprotection followed by treatment with aqueous anmumia and cation exchange afforded bismethylene analogues 259 of nucleoside triphosphate in yields up to 62%. 

A solid-phase reagent (8) has been described for the synthesis of P-triphosphate derivatives,and the benzodioxaphosphorinone, the P(iii) analogue of (6), which has previously been used for the synthesis of oligonucleotide-triphosphate derivatives, has now been used to synthesise dinucleotide tetra- and pentaphosphonates. The asymmetric bismethylene triphosphate analogue (9) has been used for the synthesis of bismethylene triphosphate analogues of nucleosides. ... 

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