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The total synthesis of Q Base (Queuine) has been accomplished in eleven steps from ribose. Mitsunobu reaction of nosyl protected amine 12 with known cyclopentenol 7, derived from ribose, gave 13, the first key intermediate in the synthesis. The pyrrolo[2,3-d]pyrimidine ring system of Q Base was built via a cyclocondensation reaction between a β-aminobromoaldehyde 16, derived from the Mitsunobu product 13, and 2,4-diamino-6-hydroxypyrimidine. Deprotection of the product from the cycloccondensation reaction (17) gave Q Base. (C) 2000 Elsevier Science Ltd.

A convenient new method for synthesizing queuine (1) pyrrolopyrimidin-4(3H)-one>, the base of the naturally occuring hypermodified nucleoside, queuosine, present in certain transfer RNAs, and its biosynthetic precursor, 2-amino-5-aminomethylpyrrolopyrimidin-4(3H)-one (2) (Pre Q1 base), was succesfully exploited.This method involved two critical rections: the Mannich reaction using dibenzylamine-formaldehyde of 2-acrylaminopyrrolopyrimidin-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-dibenzylamino 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.