We report here an efficient solid-phase synthesis of N-1-alkyl-substituted analogues of cyclic inosine-diphosphate-ribose (cIDPR), a mimic of cyclic ADP-ribose (cADPR). Our synthetic strategy makes use ofa polystyrene support to which inosine was bonded through a 20,30-acetal linkage. Insertion of a u-hy-droxy-polymethylene chain of variable length on N-1, followed by conversion into N-1-alkylinosine-bis-phosphate derivatives and cyclization, allowed to obtain analogues of cIDPR of various ring size. Thecyclization step was carried out both in solid-phase and in solution by pyrophosphate bond formation.The effect of the N-1-polymethylene chain length on the cyclization yields as well as the reactionconditions, which led to the solid-phase pyrophosphate bond formation, were thoroughly investigated.

A solid-phase approach to the synthesis of N-1-alkyl analogues of cyclic inosine-diphosphate-ribose (cIDPR)

OLIVIERO, GIORGIA;D'ERRICO, STEFANO;BORBONE, NICOLA;AMATO, JUSSARA;PICCIALLI, VINCENZO;VARRA, MICHELA;PICCIALLI, GENNARO;MAYOL, LUCIANO
2010

Abstract

We report here an efficient solid-phase synthesis of N-1-alkyl-substituted analogues of cyclic inosine-diphosphate-ribose (cIDPR), a mimic of cyclic ADP-ribose (cADPR). Our synthetic strategy makes use ofa polystyrene support to which inosine was bonded through a 20,30-acetal linkage. Insertion of a u-hy-droxy-polymethylene chain of variable length on N-1, followed by conversion into N-1-alkylinosine-bis-phosphate derivatives and cyclization, allowed to obtain analogues of cIDPR of various ring size. Thecyclization step was carried out both in solid-phase and in solution by pyrophosphate bond formation.The effect of the N-1-polymethylene chain length on the cyclization yields as well as the reactionconditions, which led to the solid-phase pyrophosphate bond formation, were thoroughly investigated.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/366466
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