Structure-catalytic activity relationships of dicyclohexylcarboxamidine analogs in phosphorylation and alkylation of nucleosides by a two-step phosphorylating agent, 2-methylthio-4H-1,3,2-benzodioxaphosphorin 2-oxide (MTBO).
Adenosine borate complex was phosphorylated and o-hydroxybenzylated by 2-methylthio-4H-1,3,2-benzodioxaphosphorin 2-oxide (MTBO) in the presence of 4-morpholine-N,N'-dicyclohexylcarboxamidine (MDC) at first to give 1-(o-hydroxybenzyl)adenosine derivative followed by the rearrangement of the benzyl group to the N-6 amino group to give N6-(o-hydroxybenzyl)adenosine 5'-S-methyl phosphorothiolate. More than 20 analogs of MDC were examined for their catalytic activity in phosphorylation and o-hydroxybenzylation of ribonucleoside by MTBO. Dicyclohexylformamidine (DCF) and n-alkylamino analogs of MDC had no effect on the o-hydroxybenzylation of ribonucleoside by MTBO, but had great effect on the phosphorylation. Dialkylamino and cyclic imino analogs of MDC had high catalytic activities to the both reaction. The dicyclohexylcarboxamidine structure of MDC gave the catalytic ability for phosphorylation by MTBO, while the morpholine moiety had great effect on the selectivity of o-hydroxybenzylation by MTBO.
D000241:Adenosine / Q000031:analogs & derivatives; D000478:Alkylation; D000578:Amidines; D007202:Indicators and Reagents; D009705:Nucleosides / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds; D010766:Phosphorylation; D013329:Structure-Activity Relationship
D000578:Amidines; D007202:Indicators and Reagents; D009705:Nucleosides; D009943:Organophosphorus Compounds; C051671:2-methylthio-4H-1,3,2-benzodioxaphosphorin 2-oxide; D000241:Adenosine