Synthesis of the Three Most Expensive l-Hexose Thioglycosides from d-Glucose

Abstract

AbstractThe biologically important l-hexoses, which are less widespread than d-hexoses, cannot be obtained from natural sources or can only be extracted very costly. Due to the complexity of their synthesis, their commercially available derivatives (which are sold mostly in free form) are also very expensive, which is further exacerbated by the current rapid rise in prices. In the present work, starting from the cheapest d-hexose, d-glucose, using inexpensive and readily available chemicals, a reaction pathway was developed in which the three most expensive l-hexoses (l-idose, l-altrose, and l-talose) were successfully prepared in orthogonally protected thioglycoside form, ready for glycosylation. The l-ido and l-talo derivatives were synthesized by C-5 epimerization of the corresponding 5,6-unsaturated thioglycosides. From the l-ido derivatives, the orthogonally protected thioglycosides of l-altrose were then prepared by C-4 epimerization. Different approaches to the preparation of the key intermediates, 5,6-unsaturated thioglycoside derivatives, were systematically investigated in the presence of various protecting groups (ether and ester) and using commercially available reagents.