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-[ (1 S,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-aminomethyIpyrrolo[2,3-~ 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-dibenzylamino function in the resulting Mannich base (1 7) with (1 S,2Rr3S) -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 b y the amine exchange reaction of (17) with appropriate amines or b y acylation of (2) with appropriate acylating agents.is the base of a hypermodified nucleoside, queuosine, located in the first position of the anticodon of tRNA molecules from various organisms, including mammalian tissues. Because of its unique structure and particular biosynthesis, much attention has been focussed on its biological function in cells, tissues, and whole mammals. ' Its functional role, however, remains to be clarified.The present study was initiated in order to obtain a sample, sufficient in amount to allow further extensive biological studies of (1) ' The first total syntheses of queuosine, queuine, and its biosynthetic precursor,2 pre Q 1 base (2) (2-amino-5-aminomethylpyrrolo[2,3-d]-pyrimidin-4(3H)-one), were achieved by Goto et ~1 . ~ However, their methods of synthesis, although elegant, require extremely lengthy and multistep procedures which are inefficient when synthesizing large quantities of (1) and its analogues for extensive biological studies.

Structure of a class II preQ1 riboswitch reveals ligand recognition by a new fold

“…1a,b) and mutants thereof were prepared by in vitro transcription and purified by denaturing PAGE as described 23 . PreQ 1 was prepared by organic synthesis 27 (LeadGen Labs, LLC). ITC measurements were conducted using a VP-ITC calorimeter (MicroCal, Inc) at 20 °C or 25 °C.…”

Hypermodification of tRNA in Thermophilic Archaea

“…General Methods and Materials-The syntheses of preQ 1 , preQ 0 , archaeosine base, and 7-formamido-7-deazaguanine were carried out as described (25,26). Protein concentrations were determined with Coomassie protein reagent (Bio-Rad) according to the method of Bradford (27), using bovine serum albumin as a standard.…”

Robust Synthesis and Crystal‐Structure Analysis of 7‐Cyano‐7‐deazaguanine (PreQ0 Base) and 7‐(Aminomethyl)‐7‐deazaguanine (PreQ1 Base)

“…To study this process in more detail, it is essential to have an efficient synthetic route to the preQ 1 base. Herein, we describe two convenient synthetic strategies together with the crystal structure of preQ 1 [11].…”