Synthesis of Structurally Simplified Aureolic Acid Aglycone-C-D-E Trisaccharide Analogues

Abstract

Syntheses of aureolic acid analogues (5) and (6) with (2S)- and (2R)-acyloin stereochemistry, respectively, are described. The synthesis of (5) utilizes a `C + DE' glycosidation sequence, whereas analogue (6), with unnatural (2R)-acyloin stereochemistry, was synthesized by a sequence in which the entire C-D-E trisaccharide was introduced in a single step. While these syntheses provided sufficient quantities of the two aureolic acid analogues for use in studies of Mg²⁺ complex formation and deoxyribonucleic acid (DNA) binding, this work also highlights certain limitations in the use of 2-thiophenyl glycosyl donors for synthesis of 2-deoxy-β-glycosides. Specifically, difficulties were encountered in the identification of a protecting group for the aglycone C8 phenol that is fully compatible with the conditions required for reductive removal of the thiophenyl substituents after completion of the glycosidation sequence. Sensitivity of the C2 acyloin stereocentre to the conditions required for deprotection of a phenolic acetate ester are also highlighted in the syntheses of (5), and especially of (6).