New Efficient Synthesis of tRNA Related Adenosines Bearing the Hydantoin Ring (ct6A,ms2ct6A) by Intramolecular Cyclization of N6-(N-Boc-α-aminoacyl)-adenosine Derivatives

A novel and efficient way for the synthesis of N⁶-hydantoin-modified adenosines, which utilizes readily available N⁶-(N-Boc-α-aminoacyl)-adenosine derivatives, was developed. The procedure is based on the epimerization-free, Tf₂O-mediated conversion of the Boc group into an isocyanate moiety, followed by intramolecular cyclization. Using this method two recently discovered hydantoin modified tRNA adenosines, that is, cyclic N⁶-threonylcarbamoyl-adenosine ( ct⁶A ) and 2-methylthio-N⁶-threonylcarbamoyladenosine ( ms²ct⁶A ) were prepared in good yields.