Synthesis of Potential Purinoceptor Antagonists: Application of P1-tBu Phosphazene Base for Alkylation of Adenine in Solution and on Solid Phase

Abstract

Alkylation of adenine in solution and on solid phase was accelerated by phosphazene base P1-tBu compared to mineral bases. The reactions in solution afforded regioselectively the appropriate N9-alkylated adenines with high preparative yields while the reaction with polystyrene resin-bound N-bromoacetylated peptides gave three regioisomers (alkylated at the N9, N7, and N3 position of adenine) in a 4:2:1 molar ratio. Ten novel nonphosphate nucleotide analogues were tested in an ADP-induced platelet aggregation assay.

Solvent‐directed Regioselective Benzylation of Adenine: Characterization of N9‐benzyladenine and N3‐benzyladenine

“…The majority of papers have identified this minor isomer to be N7-benzyladenine [10,11] while two groups identified this isomer as N3-benzyladenine [8,9]. It is commonly reported that the reaction of adenine with an alkyl halide at elevated temperatures in the presence of base yields the N9 and N7 regioisomers, whereas in the absence of base yields N3-alkylated adenine [13][14][15][16][17][18][19], and it has been reasoned that the formation of the N9/N7 regioisomers can be explained in terms of the dominance of the adenine tautomers, N9-H and N7-H [20]. Our aim was therefore to synthesize sufficient quantities of the minor benzyladenine regioisomer to allow for a full characterization by X-ray crystallography and two-dimensional NMR techniques.…”

Invited Lectures

“…Direct connection of carboxylate-containing structures to the C9-position of adenine gave a class of compounds were the ribose moiety was missing. Some of these derivatives weakly inhibited ADP induced platelet aggregation 3 . …”