Unusually Stable Picoloyl‐Protected Trimethylsilyl Glycosides for Nonsymmetrical 1,1′‐Glycosylation and Synthesis of 1,1′‐Disaccharides with Diverse Configurations

Abstract

Nonsymmetrical 1,1'-disaccharides and related derivatives constitute structural components in various glycolipids and natural products. Some of these compounds have been shown to exhibit appealing biological properties. We report a direct yet stereoselective 1,1'-glycosylation strategy for the synthesis of nonsymmetrical 1,1'-disaccharides with diverse configurations and sugar components. The strategy is based on the joined forces of a new class of configurationally stable glycoside acceptors and stereodirecting thioglycoside donors. The new glycoside acceptors feature a picoloyl (Pico) protecting group at the remote C4/C3 position that confers unusual stability on TMS glycosides under acidic conditions.

Synthesis of β‐Glucosides with 3‐O‐Picoloyl‐Protected Glycosyl Donors in the Presence of Excess Triflic Acid: Defining the Scope

“…First, we replaced TfOH with trimethylsilyl triflate (TMSOTf)w hich has been reported to coordinate to the Pico group. [9] NIS/TMSOTfpromoted reactionss howed the identical outcome( entry 3) to that achieved with NIS/TfOH (entry 1). On the other hand, NIS/ AgOTf promoted reactions afforded only am odest improvement over HAD reactions upon increase from the catalytic amount (a/b 1:2.3) to excess of AgOTf( a/b 1:7.0, entry 4).…”

Diverse Synthesis of Natural Trehalosamines and Synthetic 1,1′‐Disaccharide Aminoglycosides

“…Among the building blocks in Scheme B, C, thioglycosyl donors 22 – 24 and TMS α‐glycoside acceptors 27α , 29α , and 31α are known compounds, and their preparation followed literature procedures . The syntheses of thioglycosides 21 , 25 , and 26 ; TMS α‐glycosides 28α and 30α ; and TMS β‐glycoside 29β are outlined in Scheme A–D.…”

“…The exact temperature was optimized for each donor/acceptor pair. For example, the construction of 1α→1′α‐linked disaccharides 11 – 17 was performed at 0 °C (Table , entries 1–7), but at the same temperature, the β selectivity of a participating thio‐ d ‐ galacto ‐pyranoside donor was eroded . Therefore, for the construction of disaccharides 18 and 19 , a lower temperature of −20 °C was applied (Table , entries 8 and 9).…”

“…Recently, we developed a glycosylation method for the coupling of configuration‐stable trimethylsilyl (TMS) glycoside acceptors and stereodirecting thioglycoside donors with excellent stereocontrol . The stability of the TMS glycoside stems from a picolinoyl (Pico) group at the C4 position, which coordinates with trimethylsilyl trifluoromethanesulfonate (TMSOTf, a by‐product of the glycosylation promoter) that impedes α→β anomerization of the glycoside (Scheme A).…”

Stereoselective Synthesis of 1,1′‐Disaccharides by Organoboron Catalysis

“…So far, several efficient methods to control the stereochemistry of the anomeric centers of 1,1′‐disaccharides have been developed by using cyclic stannanes, mixed acetals, and picolyl‐protected trimethylsilyl ethers as glycosyl acceptors (Figure a). However, there is still room for further exploration of the catalytic and divergent synthesis of various 1,1′‐disaccharides from the same glycosyl acceptor.…”