Stereoselective Synthesis of Glycosyl Cyanides by TMSOTf‐Mediated Ring Opening of 1,6‐Anhydro Sugars

Abstract

We describe herein a convenient access to glycosyl cyanides by way of TMSCN ring opening of 1,6-anhydro sugars mediated by TMSOTf with modest to high stereocontrol in the D-gluco, Dgalacto and D-manno series. The reaction is tolerant to various functional groups including free alcohols, alkenes and terminal alkynes. The straightforward synthesis of a constrained analogue of 1-cyano-D-glucal with a 3,6-anhydro sugar framework is presented to illustrate the interest of the TMSCN ring-opening reaction.

From Sweet Molecular Giants to Square Sugars and Vice Versa

“…A decade later, in connection with our interest on C -glycosides and related compounds 53 76 90 (see Section 4), we applied a similar ring-opening strategy for the one-step synthesis of glycosyl cyanides from 1,6-anhydrosugars (Scheme 5a ). 91 Anomeric cyanation is indeed one of the simplest C -extension methods to access C -glycosides.…”

“…The significance of the TMSCN ring-opening reaction was illustrated by the straightforward synthesis of a constrained analogue of 1-cyano- d -glucal with a 3,6-anhydrosugar framework, a useful building block for the synthesis of constrained analogues of C -nucleosides (Scheme 5b ). 91 Having in hand a good methodology to activate the anomeric position as a glycosyl azide (‘ ON ’) from an unactivated 1,6-anhydrosugar (‘ OFF ’), we synthesized all the desired disaccharide modules activated at each or at both ends. 85 The molecular-lego strategy allowed the synthesis of close analogues of cyclodextrins following a cyclooligomerization approach and also led to acyclic alkyne-functionalized scaffolds of controlled size (Figure 6b ).…”

“…Preliminary data in an ongoing study in our laboratory indicates that the importance of the bind-and-recapture effect should not be underestimated. 59 These findings are based on a systematic SAR study conducted with the objective of addressing two questions that have emerged from our previous mechanistic study. Based on the sandwich-type model and using the 36-valent inhibitor as a starting point, would it be possible to achieve high multivalent effects using related analogues having only 4 inhitopes following a 'less-is-more' approach?…”

“…Preliminary enzymatic assays in connection with AUC-SV data provided rather unexpected results. 59 The synthesized 4-valent clusters as well as most of the corresponding 12-valent analogues led to the formation of a 1:1 complex despite the fact that they theoretically possess the key structural features (inhitope, scaffold size, linker length) to enable the formation of a sandwich-type complex. Only one highly symmetrical 12-valent cluster led to the formation of a 2:1 JB-man-inhibitor complex with, however, a decrease of one order of magnitude in the multivalent effect compared to the 36-valent cluster, as judged by the rp/n values.…”

1,2,3‐Triazole‐Containing Azamacrocycles from Chiral Triazolopeptoids: Synthesis and Solid‐State Studies

“…[13][14][15][16][17] Our choice to incorporate triazoles [12] derived from the extensive use of this heteroaromatic unit into peptide and peptoids field: [18] in fact, since the first publication by Ghadiri and coworkers, [19] this moiety, as bioisostere of amide bond, has been introduced for head-to-tail macrocyclization, side chain to-side chain connection and conjugation of ligands to the peptidomimetic skeleton. [20][21][22][23][24] The presence of the intriguing 1,2,3-triazole moiety in the oligoamide backbone further rigidifies the macrocyclic structures, amplifying, at the same time, the biomimicry potentials, thanks to its known abilities to establish hydrogen and halogen bonding and metal coordination. [25,26] With the idea to design novel nitrogen-containing macrocycles and better understand the effect of chiral side chains on the overall morphology and conformational attitudes [27] of triazolopeptoids, herein we report the synthesis of triazolopeptoid 4 and 5 containing properly arranged N-(S)-(1phenylethyl)glycine (Nspe) and benzyl side chains.…”