Nucleosides. LXV. Synthesis of New Pteridine–N₈–Nucleosides

Abstract

A general synthetic approach to various isoxanthopterin-nucleosides starting from 6-methyl-2-methylthio-4(3H),7(8H)-pterdinedione (1) has been developed. Ribosylation with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose via the silyl-method led to 2 and reaction with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-ribofuranose using the DBU-method afforded 28. Protection of the amide function at O4 by benzylation to 5 and by a Mitsunobu reaction with 2-(4-nitrophenyl)ethanol to 29 gave soluble intermediates which can be oxidized to the corresponding 2-methylsulfonyl derivatives 8 and 30, respectively. Nucleophilic displacement reactions of the highly reactive 2-methylsulfonyl functions by various amines proceeded under mild conditions to isoxanthopterin-N8-ribo- (11-17) and 2'-deoxyribomucleosides (31-33). Debenzylation can be achieve by Pd-catalyzed hydrogenation (9 to 19) and cleavage of the npe-protecting group (31, 32 to 34, 35) works well with DBU by beta-elimination.

Mitsunobu and Related Reactions: Advances and Applications

“…However, an exocyclic NHC(O)CH 3 group connected to guanosine underwent only N -alkylation leading to N 2 -alkylguanosine . In the synthesis of pteridine− N 8 −nucleosides, Pfleiderer and co-workers utilized an O -alkylation in an intermediate step for protection of an amide functionality …”

“…771 In the synthesis of pteridine-N 8 -nucleosides, Pfleiderer and co-workers utilized an O-alkylation in an intermediate step for protection of an amide functionality. 772 An interesting case of O(S)-alkylation with cyclization involved bisbenzoxazoles and bisbenzothiazoles of type 250 (Scheme 60a). 773 Here also, an NH to OH tautomerization is required prior to cyclization and crude dihydroxyaryl diimides could be used directly.…”

The diversity‐oriented synthesis of pteridines—achievements and potential for development

“…In an example bringing together alkylthio substituent chemistry with N‐alkylation, the Pfleiderer group synthesized pteridinyl nucleoside analogues with diversity at C2 and C4 (31) and related protected nucleotides in a form suitable for solid phase nucleic acid synthesis (Scheme ).…”