Synthesis of queuine, the base of naturally occurring hypermodified nucleoside (queuosine), and its analogues

Abstract

A convenient new method for synthesizing queuine (1){2-amino-5-[(1S,2R,3S)-2,3-dihydroxycyclopent-4-enylaminomethyl]pyrrolo[2,3-d]pyrimidin-4(3H)-one}, the base of the naturally occurring hypermodified nucleoside, queuosine, present in certain transfer RNAs, and its biosynthetic precursor, 2-amino-5-aminomethylpyrrolo[2,3-d] pyrimidin-4(3H)-one (2)(Pre Q1 base), was successfully exploited. This method involved two critical reactions: the Mannich reaction using dibenzylamine–formaldehyde of 2-acylaminopyrrolo[2,3-d] pyrimidin-4(3H)-one (7), which resulted in the selective introduction of the dibenzylaminomethyl group into the 5-position of (7), and an amine exchange reaction of the 5-dibenzylamine function in the resulting Mannich base (17) with (1S,2R,3S)-2,3-isopropylidenedioxycyclopent-4-enylamine, which yielded the desired queuine (1). Similar reaction of (17) with ammonia gave the biosynthetic precursor of queuine (2)(Pre Q1 base). Thus, a series of queuine analogues with structural variations in their 5-aminomethyl side-chains was synthesized by the amine exchange reaction of (17) with appropriate amines or by acylation of (2) with appropriate acylating agents.