Development of a convenient route for the preparation of the N ²-Cbz-protected guaninyl synthon required for Boc-mediated PNA synthesis

An efficient, high yielding, chemo- and regioselective, five-step synthetic route to N²-Cbz-guanin-9-yl acetic acid has been developed, which avoids the use of triphosgene. After formation of the N²-Boc protected purine from 2-amino-6-chloropurine, two successive base-controlled alkylations allowed an N⁹-tert-butyl acetate function followed by an N²-Cbz moiety to be installed. The selectivities of these reactions were confirmed through an X-ray crystallographic study of the 6-(2-nitrophenoxy) analogue. Final hydrolytic dechlorination and removal of the Boc and tert-butyl ester protecting groups were accomplished concomitantly under acidic conditions to afford the guanin-9-yl PNA monomer synthon in an overall yield of 53%. © 2013 Elsevier Ltd. All rights reserved.