Nucleoside derivatives Dinucleoside phosphates

Use of modified Swem-type conditions can give good yields ofO-methylthiomethyl (MTM) derivatives (190), which can be used to make various other derivatives such as the 3 -0-halomethyl compounds and, thence by Arbusov reactions, 3 -0-phosphonomethyl nucleosides.259 a similar 3 -0-MTM derivative was used to make the methylene analogue (191) of a dinucleoside phosphate, and a 5 -0-MTM ester of thymidine was used to link glucose and serine to 0-S of thymidine via methylene acetals.2 The spin-labelled spiroketal (192) derived from uridine has been prepared, and its e.s.r. properties studied.26l... 

The dinucleoside dipyrophosphate 81 has been obtained in 30% yield following reaction of the nucleosides with a large excess of phosphoryl chloride in trimethylphosphate/DMF. Slow decomposition of 81 produces the corresponding nucleoside 3, 5 -cyclic phosphate derivatives. 

Dinucleoside-a-hydroxybenzylphosphonates 2 in up to 90% yield were synthesized by reacting the symmetric dinucleoside H-phosphonates 1 with benzaldehyde derivative in the presence of catalytic amounts of a tertiary base like diisopropylethylamine (DIPEA), or tri-ethylamine (TEA). Dinucleoside-a-hydroxybenzylphosphonates 2 are consideied uncharged prodrugs of 5 -nucleoside H-phosphonates 3 and 5 -nucleoside monophosphates 4. These two compounds are released by controlled hydrolysis via two different pathways the phospho-nate-phosphate rearrangement and the direct cleavage mechanism [188]. 

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