On the Reactivity and Selectivity of Galacturonic Acid Lactones

The reactivity and stereoselectivity of a galacturonic acid 3,6-lactone thioglycosyl donor, previously described as a highly reactive glycosylating agent, has been investigated by using a series of competition experiments and condensation reactions with different thiophilic activator systems. It is revealed that the relative reactivity of the thioglycosides depends on the activator system used and that p-nitrophenylsulfenyl triflate shows overall attenuated reactivity differences with respect to the commonly used N-iodosuccinimide/triflic acid promoter system. With respect to the stereoselectivity of the studied galacturonic acid 3,6-lactone thioglycosyl donor, it is revealed that a preactivation-based glycosylation system gives rise to α-selective glycosylation, whereas an in situ activation protocol leads to the formation of the β-product with good selectivity. It is hypothesized that these opposingstereoselectivities are the result of different product-forming intermediates. Where preactivation of the donor leads to the formation of an intermediate β-triflate, which is substituted in a concerted fashion to provide the α-product, a 3H4 oxocarbenium ion like species is substituted in the in situ activation experiment to provide the β-linked product.