On the Reactivity and Selectivity of Galacturonic Acid Lactones

• Published in: European journal of organic chemistry 2012-10, Vol.2012 (29), p.5729-5737
• Main Authors: Christina, Alphert E., Muns, Joey A., Olivier, Jeremy Q. A., Visser, Lotte, Hagen, Bas, van den Bos, Leendert J., Overkleeft, Herman S., Codée, Jeroen D. C., van der Marel, Gijs A.
• Format: Article
• Language: English
• Subjects: Acids; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemical reactivity; Chemistry; Chemoselectivity; Diastereoselectivity; Exact sciences and technology; Glycosides; Glycosylation; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Lactones; Organic chemistry; Preparations and properties; Reactivity and mechanisms
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201200717

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. The reactivity and stereoselectivity of a galacturonic acid 3,6‐lactone thioglycosyl donor has been investigated by using thiophilic activator systems. The reactivity of the thioglycosides depend on the activator system used. The stereoselectivity arises from preactivation of the glycosylation system, giving rise to α‐selective glycosylation, whereas in situ activation gives the β‐product.