Structure and Reactivity of Glycosyl Isocyanides

Abstract

3D structural information was obtained from mono‐, di‐ and trisaccharide formamide and isocyanide derivatives by analysis of their X‐ray crystal structure and NMR spectroscopy. The isocyanide anomeric effect was observed. Data mining of the Cambridge Structural Database (CSD) was performed and statistically confirmed our findings. Application of the glycoside isocyanides in the synthesis of novel glycoconjugates as drug‐like scaffolds by MCR chemistry underscores the usefulness of the novel building blocks.

Crystal Clear: Decoding Isocyanide Intermolecular Interactions through Crystallography

“…This involves a hydrogen bond with OH at 2.5 Å and two interactions with unpolarized aliphatic CH groups at 2.8 and 2.9 Å. Another multipolar hydrogen bonding interaction occurs in β-arabinose-derived peracylated isocyanide 19 . The isocyanide C undergoes three interactions with polarized CH groups at distances between 2.7 and 2.9 Å.…”

“…In a number of crystal structures, the isocyanide C approaches a nearby carbonyl C, which can be interpreted as representatives of the Bürgi–Dunitz trajectory (Figure A–C). The Bürgi–Dunitz trajectory traces point along the pathway of bond formation between a nucleophile and an electrophile. , In a peracylated lactose derivative, β-lactosyl isocyanide 27 , the isocyanide C approaches the acetyl C within 3.3 Å, nearly perpendicular to the plane of the acetyl group with an angle (RNC···CO) of 102° . Another example of a Bürgi–Dunitz approach of an isocyanide C to a carbonyl can be observed in the structure of substituted azulene isocyanide 25 with a distance (RNC···CO) of 3.4 Å .…”

“…Another multipolar hydrogen bonding interaction occurs in β-arabinose-derived peracylated isocyanide 19 . 61 The isocyanide C undergoes three interactions with polarized CH groups at distances between 2.7 and 2.9 Å.…”

Glycoconjugates via Phosphorus Ylides

“…For example, they could be employed in the Wittig reaction, which is a well investigated reaction, extensively used for derivatization of carbohydrates, important initial reagents in the synthesis of naturally occurring compounds. In our previous studies towards glycoconjugate synthesis [31] we took advantage of our Leuckart-Wallach procedure towards glycosyl formamides which is the key intermediate, followed by their transformation to the corresponding isocyanides. transport properties through transporters and increase water solubility due to the attached sugar moieties [27,28] or more importantly in the triphenylphosphonium-based modification of molecules facilitating mitochondria targeting.…”

“…In our previous studies towards glycoconjugate synthesis [31] we took advantage of our Leuckart-Wallach procedure towards glycosyl formamides which is the key intermediate, followed by their transformation to the corresponding isocyanides. As described before, [30,31] we performed the regio-and stereospecifically reductive amination on the 1-OH-unprotected sugars 1, affording the corresponding glucosyl (2a), galactosyl (2b), lactosyl (2c) and maltotriosyl (2d) formamides as -anomers with Z-configuration in good yields. However, in the current study we employed the glycosyl formamide directly into a MCRs, via phosphorus ylides, exploiting its acidic N-H (Figure 1B, Figure C).…”