Synthesis of rigid p-terphenyl-linked carbohydrate mimetics.

Maja Kandziora,Hans-Ulrich Reissig

doi:10.3762/bjoc.10.182

Abstract

An approach to β-D-2-aminotalose- and β-D-2-aminoidose-configured carbohydrate mimetics bearing a phenyl substituent is described. Unnatural divalent rigid p-terphenyl-linked C-aryl glycosides with 2.0 nm dimension are available using Suzuki cross-couplings. The key compound, a p-bromophenyl-substituted 1,2-oxazine, was prepared by a stereoselective [3 + 3]-cyclization of a D-isoascorbic acid-derived (Z)-nitrone and lithiated TMSE-allene. The Lewis acid-induced rearrangement of this heterocycle provided the corresponding bicyclic 1,2-oxazine derivative that may be regarded as internally protected amino sugar analogue. After subsequent reduction of the carbonyl group, the resulting bicyclic compound was used for Suzuki cross-couplings to form biphenyl aminopyran or p-terphenyl-linked dimers. Hydrogenolysis afforded new unnatural aminosugar mimetics. Zinc in the presence of acid or samarium diiodide were examined for the N–O bond cleavage in order to obtain the rigid p-terphenyl-linked C-glycosyl dimers.

Highlights

Carbohydrates are the class of biomolecules with the highest structural diversity [1,2]
In this report we present methods for the synthesis of divalent compounds 1 with p-terphenyl spacers and of β-D-2-aminotalose- or β-D-2-aminoidose-configured carbohydrate mimetics 2 (Scheme 1)
To prepare phenyl-substituted aminopyrans the N–O bond of bicyclic compounds 15a and 15b was cleaved by Scheme 5: Synthesis of bicyclic ketone 11 by Lewis acid-induced rearrangement and reduction to alcohols 12a and 12b and protection of 12a to 1,2oxazine derivative 13

Summary

Introduction

Carbohydrates are the class of biomolecules with the highest structural diversity [1,2]. In this report we present methods for the synthesis of divalent compounds 1 with p-terphenyl spacers and of β-D-2-aminotalose- or β-D-2-aminoidose-configured carbohydrate mimetics 2 (Scheme 1). The subsequent protection of the primary hydroxy group as TBS ether under standard conditions provided 11 in very good yields of up to 82% (Scheme 5).

Results

Conclusion