Optimized Conditions for the Palladium‐Catalyzed Hydrogenolysis of Benzyl and Naphthylmethyl Ethers: Preventing Saturation of Aromatic Protecting Groups

Abstract

While carrying out palladium‐catalyzed hydrogenolysis to deprotect synthetic oligosaccharides, saturation of the benzyl and naphthylmethyl ether groups to their corresponding ether was observed. In order to suppress this unwanted hydrogenation, we report a scalable practical approach using a catalyst pre‐treatment strategy, which is effective under batch or continuous flow conditions. This suppressed the unwanted hydrogenation side‐products and created a selective catalyst for hydrogenolysis of benzyl and naphthylmethyl ethers. We demonstrate the efficient deprotection of a set of structurally diverse oligosaccharides (5 examples, > 73 %).

Chemical synthesis of glycans up to a 128-mer relevant to the O-antigen of Bacteroides vulgatus

“…It is noteworthy that the 15% yield achieved for the deprotection of 128-mer (14→7) corresponds to an average~99.4% yield for each cleavage of the 322 C-O bonds. Thus far, hydrogenolysis of benzyl ethers has been employed as the final step in all the synthesis of long glycans over 50-mer, however, cautiousness remains for this transformation which could require tedious exploration of the reaction conditions 38 . 3The gold(I)-catalyzed glycosylation reaction, involving α-rhamnopyranosylation, is both stereospecific (in the presence of a neighboring-participating benzoyl group) and high-yielding.…”

Antibodies to the Cryptococcus neoformans Capsule have Innate Glycosidase Activity

“…Building blocks were synthesized as described previously. 20,24,28,51 Growth Conditions C. neoformans Molecular modelling GLYCAM carbohydrate builder was used to construct ligands and auto-dock vina for antibody docking studies, both of which can be accessed at glycam.org. [32][33][34] PyMOL was used for visualisation and figure creation.…”

“…Synthesis and assembly of the required building blocks for GXM assembly followed published protocols. 20,[23][24][25][26][27][28] Through a convert building block approach we achieved the synthesis of the bifunctionally armed decasaccharide (assembly of Compounds 1-13, Supplementary Figure 1).…”

Illuminating glycoscience: synthetic strategies for FRET-enabled carbohydrate active enzyme probes

“…69 Scheme 10 highlights the synthesis, starting from tetrasaccharide 57, which underwent iterative coupling/ deprotection sequences with glycosyl donors 58 and 59, to reveal a protected decasaccharide 60. This material was then globally deprotected using a pre-treated palladium catalyst, 70 and consecutively conjugated with FRET donor and acceptor components to reveal probe 56. The non-acetylated probe 55 was accessed by removal of the acetyl groups from 56.…”