Shelf-Stable 3-Thiocresyl-Prop-1-Enyl (TCP) Glycosides in Oligosaccharide Synthesis

Transformation of the allyl glycosides to a glycosylation-active 3-thiocresyl-prop-1-enyl (TCP) glycosides is reported herein, in an effort to devise a shelf-stable, active vinyl glycoside. Remote electrophilic activation with an iodonium source results in the formation of a glycosylation-active moiety. The efficiency of the TCP glycoside donor is demonstrated through the synthesis of a panel of di- and trisaccharides of pyranosides and furanosides, including globo-trioside Gb₃ antigen, wherein a disarmed TCP glycoside is converted facile to an armed TCP glycosyl donor, further ascertaining the tolerance towards protecting group manipulations. In addition, the synthetic utility of the TCP glycoside donor is demonstrated through the syntheses of biologically relevant tri- and hexasaccharide oligomannans, thereby establishing the potential of this new TCP glycosyl donor for oligosaccharide synthesis. Mechanistic studies reveal the remote activation of the thioether moiety by promoters, as evidenced through identification of the thioether and acrolein by-products arising from the reaction. Further, the applicability of TCP glycosides as glycosyl acceptors is also verified in glycosylations involving glycosyl halide donors. The facile isomerization of allyl glycoside, remarkable shelf-stability, tolerance towards protecting groups and applicability as a glycosyl donor, as well as glycosyl acceptor offer key advantages to TCP glycosides.