Synthesis and Deprotection of Biodegradably and Thermally Protected Dinucleoside-2 ',5 '-Monophosphate Prodrug Model of 2-5A

: Kiuru E, Malmikare S, Ora M

Publisher: WILEY-V C H VERLAG GMBH

: Zurich

: 2017

: Chemistry and Biodiversity

: CHEMISTRY & BIODIVERSITY

: CHEM BIODIVERS

: ARTN e1700220

: 14

: 9

: 10

: 1612-1872

: 1612-1880

DOI: https://doi.org/10.1002/cbdv.201700220(external)

Protected dinucleoside-2',5'-monophosphate has been prepared to develop a prodrug strategy for 2-5A. The removal of enzymatically and thermally labile 4-(acetylthio)-2-(ethoxycarbonyl)-3-oxo-2-methylbutyl phosphate protecting group and enzymatically labile 3'-O-pivaloyloxymethyl group was followed at pH 7.5 and 37 degrees C by HPLC from the fully protected dimeric adenosine-2',5'-monophosphate 1 used as a model compound for 2-5A. The desired unprotected 2,3-O-isopropylideneadenosine-2',5'-monophosphate (9) was observed to accumulate as a major product. Neither the competitive isomerization of 2',5'- to a 3',5'-linkage nor the P-O5' bond cleavage was detected. The phosphate protecting group was removed faster than the 3'-O-protection and, hence, the attack of the neighbouring 3'-OH on phosphotriester moiety did not take place.