Regioselective Strategies Mediated by Lanthanide Triflates for Efficient Assembly of Oligomannans

Abstract

Readily prepared mannosyl n-pentenylorthoesters (NPOEs) serve as donors in themselves and as convenient intermediates for other glycosyl donors, such as n-pentenyl glycosides (NPGs), thioglycosides, and trichloroacetimidates. These various donors are activated by different reagents, and are therefore amenable to versatile, discriminate use. Scandium and ytterbium triflates respond very differently to these donors, with the result that chemoselective discrimination between NPOEs, NPGs, trichloroacetimidates as well as ethyl and phenyl thioglycosides can be achieved. Appropriate NPOEs are also able to provide 2,6 and 3,6 diol acceptors via rearrangement or glycoside formation, and these can be used for one-pot, sequential glycosidations based on orthogonal donors, and in situ double differential glycosidations. Thus NPOEs activated by iodonium ion, specifically generated from ytterbium triflate/N-iodosuccinimide, can be used to monoglycosidate the diols rapidly, with exquisite regio, and sometimes chemo, selectivity. The residual NPOE is converted into disarmed NPG, which is refractory to the reaction conditions, and so poses no threat to the free-OH of the monoglycosidation product. Further glycosidation of the latter can then achieved by direct addition of a trichloroacetimidate or ethyl thioglycoside. This basic strategy has been used to prepare a branched chain pentadecamannan. The success is an example of the efficiency of donor/acceptor MATCH concept for regioselective glycosylation.

New Principles for Glycoside‐Bond Formation

“…[5] The versatility of NPOE donors was further demonstrated recently in the efficient assembly of a pentadecamannan. [121] In this synthesis, NPOEs served not only as donors, but also as convenient intermediates in the generation of other glycosyl donors, such as trichloroacetimidates, thioglycosides, and NPGs. Propargyl 1,2-orthoesters, such as 51, have also been reported recently as glycosyl donors (Scheme 7 d).…”

Neue Prinzipien für die Bildung von glycosidischen Bindungen

“…Die Vielseitigkeit der NPOE‐Donoren wurde vor kurzem bei der effizienten Herstellung eines Pentadecamannans erneut belegt,121 indem NPOEs nicht nur als Donoren fungierten, sondern auch als geeignete Intermediate für andere Glycosyldonoren, z. B. Trichloracetimidate, Thioglycoside und NPGs.…”

Experimental observations on the regioselectivity of glycosylation of a 4,6-diol system in the β-d-mannopyranosyl unit of a N-glycan pentasaccharide core structure

“…Besides, the complexity of the system further complicates attempts of rationalization. Fraser-Reid et al, who have addressed more systematically the regioselective glycosylation of diol systems, [31][32][33][34][35][36] has suggested that primary hydroxyl groups can only be considered more reactive than secondary hydroxyl groups in reaction with disarmed glycosyl donors and orthoesters and that armed glycosyl donors can favour glycosylation at the secondary rather than the primary position. 33 Our present data do not permit any interpretation of the obtained results on the basis of this suggestion.…”