The formation of symmetrical glycosyl glycuronates by direct oxidation of partially protected methyl α-D-glycopyranosides

Giovanna Cupone,Antonio De Nino,Giovanni Sindona,Renato Dalpozzo,Antonio Procopio,Loredana Maiuolo,Anthony Waring

doi:10.3998/ark.5550190.0003.b12

Abstract

The formation of symmetrical glycuronates by oxidation of methyl α-D-2,3,4-tri-O-benzoyl glycopyranosides with pyridine dichlorochromate is described. A key intermediate in the process is represented by the initially formed aldehydes which react further through two competing reaction pathways leading to the glycals and to the symmetrical esters. The symmetrical glycuronates are formed by oxidation of the corresponding hemiacetal intermediates. The absolute configuration of the chiral centers at position 2-, 3-, and 4- of the glycopyranosides does not affect the two competing reaction paths.

Highlights

In the course of our studies concerning the synthesis of analogues of antiviral nucleoside drugs[1] we planned the formation of chiral nitrones 5 from the fully protected glucopyranoside 1a through its stable 4,5- glucal, 3a, achievable through a previously reported[2] procedure (Scheme, path a)
The project aimed at exploiting new approaches to the enantioselective synthesis of isoxazolidino-nucleosides[3] after the modification of the hexose ring through conventional chemistry
Methyl α-D-2,3,4-tri-O-benzoyl glucopyranoside 1a was obtained in three steps, from the corresponding methyl α-D-glucopyranoside, by tritylation in pyridine (75% yield) followed by benzoylation in the same solvent (88% yield) and final de-blocking with trifluoroacetic acid at 0° C (85% yield)

Summary

Introduction

In the course of our studies concerning the synthesis of analogues of antiviral nucleoside drugs[1] we planned the formation of chiral nitrones 5 from the fully protected glucopyranoside 1a through its stable 4,5- glucal, 3a, achievable through a previously reported[2] procedure (Scheme, path a). The project aimed at exploiting new approaches to the enantioselective synthesis of isoxazolidino-nucleosides[3] after the modification of the hexose ring through conventional chemistry. Methyl α-D-2,3,4-tri-O-benzoyl glucopyranoside 1a was obtained in three steps, from the corresponding methyl α-D-glucopyranoside, by tritylation in pyridine (75% yield) followed by benzoylation in the same solvent (88% yield) and final de-blocking with trifluoroacetic acid at 0° C (85% yield). The corresponding N-benzyl nitrone 5 was obtained in satisfactory yield (Scheme)

PCC b

Reagents Aldehyde Ester

Findings

Experimental Section