Reactivity, Selectivity, and Synthesis of 4‐C‐Silylated Glycosyl Donors and 4‐Deoxy Analogues

Abstract

A method for introducing dimethylphenylsilyl at the 4‐position in carbohydrates has been developed. Two C‐silylated glycosyl donors were prepared via levoglucosenone, starting from cellulose. The glycosylation properties were studied using three glucoside acceptors, a 3‐OH, 4‐OH, and 6‐OH. Compared with the 4‐deoxy variant, it was found that the anomeric selectivity was influenced more by the C‐2 substituents orientation than the silyl in the 4‐position. In general, the reactivity of these donors was higher than the corresponding 4‐deoxy‐analogue, albeit a competition experiment showed that the introduction of a C−Si increases the relative reactivity by a modest factor of around two.

Green Drug Discovery: Novel Fragment Space from the Biomass-Derived Molecule Dihydrolevoglucosenone (CyreneTM)

“…In all, we selected a synthetic strategy mostly based on two key building blocks, i.e., 2 and 4. Alcohol 2 was prepared on a large scale by NaBH 4 -based reduction of Cyrene, affording an inseparable ~9/1 mixture of diastereomers with the endo isomer reportedly being the major product, which we confirmed (vide infra) [53]. Exo-amine 4 has been reported through a 4-step synthesis route starting from LGO [46], and can also be accessed from LGO by an enzymatic transamination reaction as part of a process recently awarded the Peter J. Dunn Award for Green Chemistry 2022 [48,54].…”

“…For representative benzyl ether 5a, 1D Nuclear Overhauser Effect (NOE) NMR analyses indeed indicate endo stereochemistry. As a further confirmation, the major 1 H and 13 C NMR signals for 5a are identical to those reported for the endo isomer [53], while the minor 13 C NMR signals in 5a match those reported for the exo isomer ( 1 H NMR data have not been reported for the exo isomer) [57]. Assignment of the stereochemistry in N-analogs proved to be more challenging, and success varied for several reasons: (1) As the d.r.…”

“…In the case where a library member consisting of a diastereomeric mixture gives a hit, additional efforts can separate the single diastereomers for further assays. The resulting 100-membered library comprises only novel compounds, except for 5a and the very recently disclosed 8s [ 48 , 53 ] , thus addressing unexplored parts of chemical space.…”

Advances in glycoside and oligosaccharide synthesis

“…226 Subsequent efforts to quantify this effect enabled one-pot syntheses of oligosaccharides. [227][228][229][230][231] The systematic quantification of donor reactivity established an extensive series of relative reactivity values (RRVs) for thioglycosides as the foundation for the 'programmable' one-pot synthesis of complex oligosaccharides. The sequential addition and activation of mono-hydroxylated donors in a reaction flask resulted in a growing oligomeric chain.…”

Silylated Sugars – Synthesis and Properties

“…However, we were determined to introduce a silyl group onto a structure as close to native as possible. 84 A broad variety of methods for coupling silicon and carbon exists in the literature. Of the methods mentioned in this Account, C-H activation is the only direct silicon to carbon coupling.…”