1259402-33-9Relevant academic research and scientific papers
Synthesis and Deprotection of Biodegradably and Thermally Protected Dinucleoside-2′,5′-Monophosphate Prodrug Model of 2-5A
Kiuru, Emilia,Malmikare, Suvi,Ora, Mikko
, (2017/09/18)
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?°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.
Synthesis and enzymatic deprotection of biodegradably protected dinucleoside-2′,5′-monophosphates: 3-(Acetyloxy)-2,2- bis(ethoxycarbonyl)propyl phosphoesters of 3′-O-(acyloxymethyl)adenylyl- 2′,5′-adenosines
Kiuru, Emilia,Ora, Mikko,Beigelman, Leonid,Blatt, Lawrence,Loennberg, Harri
, p. 266 - 286 (2011/10/05)
As a first step towards a viable prodrug strategy for short oligoribonucleotides, such as 2-5A and its congeners, adenylyl-2′, 5′-adenosines bearing a 3-(acetyloxy)-2,2-bis(ethoxycarbonyl)propyl group at the phosphate moiety, and an (acetyloxy)methyl- or a (pivaloyloxy)methyl- protected 3′-OH group of the 2′-linked nucleoside have been prepared. The enzyme-triggered removal of these protecting groups by hog liver carboxyesterase at pH 7.5 and 37° has been studied. The (acetyloxy)methyl group turned out to be too labile for the 3′-O-protection, being removed faster than the phosphate-protecting group, which results in 2′,5′- to 3′,5′-isomerization of the internucleosidic phosphoester linkage. In addition, the starting material was unexpectedly converted to the 5′-O-acetylated derivative. (Pivaloyloxy)methyl group appears more appropriate for the purpose. The fully deprotected 2′,5′-ApA was accumulated as a main product, although, even in this case, the isomerization of the starting material takes place.
