Diastereo- and Enantioselective Synthesis of 1′-C-BranchedN,O-Nucleosides

Abstract

A synthetic approach towards 1'-C-branched N,O-nucleosides is reported, based on 1,3-dipolar cycloaddition of ethoxycarbonylnitrone. The asymmetric version of the process exploits the presence of a chiral auxiliary at the carbon atom of nitrone and leads to beta-D and beta-L nucleosides in good yields.

Synthesis and Absolute Configuration of Novel N,O-Psiconucleosides Using (R)-N-Phenylpantolactam as a Resolution Agent

“…Attempts to carry out the reduction of the ester function of 20 with NaBH 4 in MeOH at 0 °C for 30 min, as described in a related case, , left the starting compound unchanged. When this reaction was carried out at 50 °C for 48 h, transesterification took place, the methyl ester (−)- 18 being formed.…”

“…To the best of our knowledge, the sole groups that have reported the synthesis of N , O -psiconucleosides (Figure ) both in racemic – and in enantiopure form are those of Chiacchio, Romeo, and Merino, who developed a synthetic procedure based on the 1,3-dipolar cycloaddition of a suitable nitrone with a 2-(acetoxy)acrylate, followed by a Vorbrüggen nucleosidation and NaBH 4 reduction of the ester group at the anomeric position to a hydroxymethyl function. The 1,3-dipolar cycloadditions carried out for the synthesis of these compounds proceeded with cis / trans selectivities ranging from 2.5:1 to 8.6:1.…”

Truncated phosphonated C-1′-branched N,O-nucleosides: A new class of antiviral agents

“…[6][7][8][9][10][11] Our research group has reported a versatile route towards the synthesis of N,O-psiconucleosides both in racemic and in enantiopure form. 5,[12][13][14][15] More recently, the use of a chiral auxiliary has promoted the enantioselective synthesis of a series of psiconucleosides. 16 However, none of the reported compounds has shown a remarkable biological activity, probably due to the lack of efficient phosphorylation towards the triphosphate derivatives, the active form of nucleoside RT inhibitors.…”