Gold(I)-Catalyzed Glycosylation with Glycosyl Ynenoates as Donors

Abstract

A simple and versatile glycosylation method with both armed and disarmed glycosyl ynenoates as donors is developed. Employing a gold­(I) complex as catalyst with or without the assistance of TfOH, the scope of the present glycosylation protocol is very wide. The utility of the present ynenoate donors is demonstrated in the efficient synthesis of oligosaccharides via the latent-active strategy and the multiple orthogonal one-pot strategy. Finally, this approach enables the formal synthesis of the tetrasaccharide hapten of Streptococcus pneumoniae serotype 3 and the highly convergent synthesis of the 32mer polymannoside.

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

“…The synthesis of glycans up to a 128-mer ( 7 ) consisting of disaccharide repeating unit of [→4)-α-Rha-(1 → 3)-β-Man-(1 → ] n have been achieved. The present success is attributable to the following aspects: (1) The strategic [2 n + 2 n ] glycosylation enables exponential growth of the glycan sizes 17 , leading to 128-mer via only six repetitive cycles of transformations, and ready separation of the double-sized products from the remaining and decomposed substrates. The heroic syntheses of a linear 50-mer 13 and a 100-mer 18 via step-wide glycosylation demanded exhaustive reactions (glycosylation and capping on a solid support) at each step; while the synthesis of the 151-mer 18 and 92-mer 14 took advantage of multifold glycosylations to install the identical branches.…”

“…The chemical synthesis of long glycans has been limited by the notorious low efficiency of the glycosidic coupling and protecting group manipulations. Consequently, glycans containing over 20 monosaccharide units have been synthesized only occasionally [5][6][7][8][9][10][11][12][13][14][15][16][17][18] , contributing to the general idea that chemical synthesis of long glycans are not yet of practical usefulness 19 . In this regard, a paradigm shift in the functional studies of long glycans with precise structures requires the advancement of feasible approaches to their preparation, bringing innovation to the conventional synthetic carbohydrate chemistry 20,21 .…”

Progress and challenges in the synthesis of sequence controlled polysaccharides

“…The synthesis of α-mannosides is widely established, allowing the chemical synthesis of the longest polysaccharide to date (i.e., 151mer). To speed up and simplify the solution phase synthesis of long and well-defined polymannosides, iterative coupling strategies are generally adopted [ 271 – 272 ]. Two monosaccharides are coupled yielding a disaccharide, which is parted and converted to the new donor and acceptor.…”

“…This process is repeated iteratively allowing for an exponential length growth, while maintaining control over the elongation. Beside more common LGs such as phosphates, thioethers, and imidates, ynenoate donors activated using Au(I) catalysis were successfully employed in an iterative strategy, enabling the synthesis of a 32mer [ 272 ]. The construction of α(1–6)-mannans (up to 10mer) bearing α(1–2)-Man branches was also accomplished using phosphate, N -phenyltrifluoroacetimidate or n -pentenylorthoester donors [ 273 – 274 ].…”

Cycloisomerization of π‐Coupled Heteroatom Nucleophiles by Gold Catalysis: En Route to Regiochemically Defined Heterocycles

“…As rationalized by the authors, the reaction starts with Au(I)‐mediated 6‐ endo ‐ dig selective cyclization 109 a trailed by nucleophilic attack on 109 b . On an application side, this sort of chemistry is immensely used in the alkylation of sugar derivatives and valuable fine‐chemicals [213–232] …”