Synthesis of New Acadesine (AICA-riboside) Analogues Having Acyclic d-Ribityl or 4-Hydroxybutyl Chains in Place of the Ribose

Abstract

Abstract:The antiviral activity of certain acyclic nucleosides drew our attention to the fact that the replacement of the furanose ring by an alkyl group bearing hydroxyl(s) could be a useful structural modification to modulate the biological properties of those nucleosides. Herein, we report on the synthesis of some novel acadesine analogues, where the ribose moiety is mimicked by a D-ribityl or by a hydroxybutyl chain.

Synthesis and Biological Evaluation of a New Structural Simplified Analogue of cADPR, a Calcium-Mobilizing Secondary Messenger Firstly Isolated from Sea Urchin Eggs

“…The two isomers were clearly distinguished by comparison of their 1 H-NMR spectra. In fact, in the O6 isomer the CH 2 attached to the purine O6 atom resonated as a triplet at 4.5 ppm, whereas in the N1 isomer ( 21 ) the CH 2 attached to the purine N1 atom resonated as a multiplet at 4.0 ppm, according to our previous findings [ 40 , 41 , 42 , 43 , 44 , 45 ]. With the aim of improving the yield and the regioselectivity of the reaction toward the required N1 alkylated isomer 21 , the reactivity of the soft iodide 19 was explored.…”

Synthesis of cyclic N1-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

“…In particular, the N1, N9 and C8-substituted cIDPR were the most interesting [ 24 – 33 ]. In the last few years several cIDPR analogues were also synthesized in our laboratory [ 34 – 37 ]. Among these, the N 1 -pentyl analogue cpIDP ( 3 , Fig.…”

5′-Chloro-5′-deoxy-2′,3′-O-isopropylidene-6-fluoro nebularine

“…The AMPK pathway is also implicated in the regulation of cell proliferation, and activation by AICAR could result in pro-apoptotic effects [10]. Given the importance of such a molecule, the synthesis of novel AICAR analogues is an appealing goal to better understand its mechanism of action [11][12][13][14][15]. Considering AICAR's low intestinal absorption and poor penetration of the blood-brain barrier, we synthesized a more lipophilic analogue, where the 5′-OH group was replaced by a fluorine atom (2, 5′-F-AICAR) [16].…”