Indolylthio Glycosides As Effective Building Blocks for Chemical Glycosylation

Abstract

The S-indolyl (SIn) anomeric moiety was investigated as a new leaving group that can be activated for chemical glycosylation under a variety of conditions including thiophilic and metal-assisted pathways. Understanding of the reaction pathways for the SIn moiety activation was achieved via the extended mechanistic study. Also reported is how the new SIn donors fit into selective activation strategies for oligosaccharide synthesis.

N‐Alkylated Analogues of Indolylthio Glycosides as Glycosyl Donors with Enhanced Activation Profile

“…of AgOTf as promoter. These reaction conditions are standard for the activation of Sbox glycosides, [22] but unmodified SIn glycosides reacted very slowly, even in the presence of a large access of AgOTf [7] . Thus, a competition reaction between SinMe donor 5 and Sbox donor 34 resulted in a complete consumption of donor 34 in 5 min.…”

“…We chose to explore the same activators as those used for regular (NH) thioindole glycosyl donors, i. e. NIS/TfOH, NIS/TMSOTf and Ag 2 CO 3 /TMSOTf. [7] Glycosidation of donor 2 with acceptor 13 in the presence of 3.0 equiv. NIS and 0.8 equiv.…”

“…[6] Our recent endeavor was dedicated to studying (1H-indol-2yl)thio (S-indolyl, SIn) glycosides. [7] These compounds are structurally similar both to thioglycosides and to thioimidates, but in terms of reactivity act as neither due to their unusual activation profile. In fact, SIn glycosides were found to be fully orthogonal in respect to ethylthio glycosides.…”

Transition‐Metal‐Mediated Glycosylation with Thioglycosides

“…Demchenko and co‐workers introduced indolylthio glycosyl (SIn) donors that can be activated with AgBF 4 and Ag 2 CO 3 /TMSOTf among other conditions [107] . Several glycosyl donor – acceptor combinations have been investigated, among these, glycosylation of 2‐OH acceptor 93 with armed SIn glucosyl donor 92 in presence of Ag 2 CO 3 /TMSOTf produced product 94 in 81 % yield (Scheme 13B).…”

“…Demchenko and co-workers introduced indolylthio glycosyl (SIn) donors that can be activated with AgBF 4 and Ag 2 CO 3 / TMSOTf among other conditions. [107] Several glycosyl donoracceptor combinations have been investigated, among these, glycosylation of 2-OH acceptor 93 with armed SIn glucosyl donor 92 in presence of Ag 2 CO 3 /TMSOTf produced product 94 in 81 % yield (Scheme 13B). Although activation of the moiety SIn required excess reagents, activation was found to be completely orthogonal in respect to building blocks equipped with SEt and SBox leaving groups.…”