Aralkylation of Guanosine With Para-Substituted Styrene Oxides

To probe mechanisms of nucleoside aralkylation, product distributions and product stereochemistries were determined in reactions of optically active p-methyl-and p-bromostyrene oxide with guanosine. The proportion of 7-, N-2- and O-6-substituted guanosine products was similar to 0.32:0.62:0.06 in neutral, aqueous reactions with the (R)-p-methylstyrene oxide and similar to 0.85: 0.09:0.04 in reactions with the (R)-p-bromostyrene oxide. The exocyclic positions opened the epoxide at the alpha-carbon. Epoxide ring opening by the nitrogen at the 7-position showed little preference for the alpha- or beta-carbons in reactions with p-methylstyrene oxide. However, the p-bromostyrene oxide favored reaction at the beta-carbon almost 4-fold over reaction at the alpha-carbon. Almost total inversion of stereochemistry was found to occur in reactions at the 7-position. In contrast, the ratio of inversion to retention of configuration in N-2- and O-6-substituted products was similar to 2:1 and similar to 1:1 for reactions with the p-methylstyrene oxide and similar to 6:1 and similar to 3:1 for reactions with p-bromostyrene oxide, respectively. These experiments suggest that an S(N)2 mechanism is in effect with reactions at the 7-position, whereas substrates of an increasingly ionic nature are involved in reactions at the N-2- and O-6-positions, respectively. [References: 35]

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