Synthesis of 4-thio-d-glucopyranose and interconversion to 4-thio-d-glucofuranose
Jack Porter, Marcelo A. Lima, Imlirenla Pongener, Gavin J. Miller
Abstract
Sulfur containing glycosides offer an exciting prospect for inclusion within noncanonical glycan sequences, particularly as enabling probes for chemical glycobiology and for carbohydrate-based therapeutic development. In this context, we required access to 4-thio-d-glucopyranose and sought its chemical synthesis. Unable to isolate this material in homogenous form, we observed instead a thermodynamic preference for interconversion of the pyranose to 4-thio-d-glucofuranose. Accordingly, we present an improved method to access both bis(4-thio-d-glucopyranoside)-4,4′-disulfide and 4-thio-d-glucofuranose from a single precursor, demonstrating that the latter compound can be accessed from the former using a dithiothreitol controlled reduction of the disulfide. The dithiothreitol-mediated interconversion between pyranose (monomer and disulfide) and furanose forms for this thiosugar is monitored by 1H NMR spectroscopy over a 24-h period. Access to these materials will support accessing sulfur-containing mimetics of glucose and derivatives therefrom, such as sugar nucleotides.