A Selective Procedure for 6-Subsituted Pterin Derivatives: Synthesis and Substitution of Pterin 6-Triflate
Introduction of a C(6) side chain on the pterin skeleton with regioselective manor is one of most challenging subjects in the field of pteridine chemistry (1). Among procedures for 6-substituted pteridines, substitution reaction of 6-halogenated pteridines by an organic group has succeeded to synthesize valuable naturally occurring pterins and their derivatives (2–6). However, in such halogenated pterins, the general nucleophilic substitution (SN1 or SN2 reaction) by carbon nucleophiles like enolate ions and carbanions did not occur in the absence of accelerators (7). Previously we described that the nucleophilic substitution of lumazine 6-triflate by various carbon reagents proceeded to give 6-substituted pteridine derivatives in high yields (8–10). On the other hand, the selectivity of the oxidation which is the important step in the preparation of a pteridine triflate toward its N-oxide is different, and, in addition, the amino group on the C(2) position is labile under acidic conditions employed to the conversion of N-oxide to the triflate. Therefore, it seemed to be difficult to apply the methodology for lumazine 6-triflate to pterin. We would like to describe in this paper a selective synthesis of the pterin 6-triflate and its application to syntheses of 6-substituted pterins.
KeywordsHydrolysis Hydrogen Peroxide Magnesium Acetonitrile Folate
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