Chemical Synthesis of Human Milk Oligosaccharides: para-Lacto-N-hexaose and para-Lacto-N-neohexaose.

Human milk oligosaccharides (HMO) have emerged as a very active area of research in glycoscience and nutrition. HMO are involved in the early development of infants and may help to prevent certain diseases. The development of chemical methods for obtaining individual HMO aids the global effort dedicated to understanding the roles of these biomolecules. Reported herein is the chemical synthesis of two common core hexasaccharides found in human milk, i. e. para-lacto-N-hexaose (pLNH) and para-lacto-N-neohexaose (pLNnH). After screening multiple leaving groups and temporary protecting group combinations, a 3+3 convergent coupling strategy was found to work best for obtaining these linear glycans.

Chemical synthesis of human milk oligosaccharides: lacto-N-neohexaose (Galß1 → 4GlcNAcß1→)2 3,6Galß1 → 4Glc.

The first chemical synthesis of lacto-N-neohexaose (LNnH) has been completed using a convergent synthetic strategy. The reaction conditions and donor-acceptor combinations have been carefully refined to minimize side reactions and achieve high yields in all glycosylation steps. Lacto-N-neotetraose, another common human milk oligosaccharide, was also synthesized en route to the target LNnH.

Picoloyl protecting group in synthesis: focus on a highly chemoselective catalytic removal.

The picoloyl ester (Pico) has proven to be a versatile protecting group in carbohydrate chemistry. It can be used for the purpose of stereocontrolling glycosylations via an H-bond-mediated Aglycone Delivery (HAD) method. It can also be used as a temporary protecting group that can be efficiently introduced and chemoselectively cleaved in the presence of practically all other common protecting groups used in synthesis. Herein, we will describe a new method for rapid, catalytic, and highly chemoselective removal of the picoloyl group using inexpensive copper(ii) or iron(iii) salts.

Chemical Synthesis of Human Milk Oligosaccharides: Lacto-N-hexaose Galß1→3GlcNAcß1→3 [Galß1→4GlcNAcß1→6] Galß1→4Glc.

The first synthesis of lacto-N-hexaose (LNH) has been completed using a convergent strategy. The donor-acceptor protecting-leaving group combinations were found to be of paramount significance for achieving successful glycosylations and minimizing side reactions. Lacto-N-tetraose, another common human milk oligosaccharide, was also obtained en route to the target LNH.

S-Benzimidazolyl (SBiz) Imidates as a Platform for Oligosaccharide Synthesis via Active-Latent, Armed-Disarmed, Selective, and Orthogonal Activations.

This article describes the development of S-benzimidazolyl (SBiz) imidates as versatile building blocks for oligosaccharide synthesis. The SBiz imidates have been originally developed as a new platform for active-latent glycosylations. This article expands upon the utility of these compounds. The application to practically all common concepts for the expeditious oligosaccharide synthesis including selective, chemoselective, and orthogonal strategies is demonstrated. The strategy development was made possible thanks to our enhanced understanding of the reaction mechanism and the modes by which SBiz imidates interact with various promoters of glycosylation.

Conformationally superarmed S-ethyl glycosyl donors as effective building blocks for chemoselective oligosaccharide synthesis in one pot.

A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete ß-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning.

The chemical synthesis of human milk oligosaccharides: Lacto-N-neotetraose (Galß1→4GlcNAcß1→3Galß1→4Glc).

The discovery of innovative methods that offer new capabilities for obtaining individual oligosaccharides from human milk will help to improve understanding their roles and boost practical applications. The total chemical synthesis of lacto-N-neotetraose (LNnT) has been completed using both linear and convergent strategies. The donor and acceptor protecting and leaving group combinations were found to be of paramount significance to successful couplings.

The chemical synthesis of human milk oligosaccharides: Lacto-N-tetraose (Galß1→3GlcNAcß1→3Galß1→4Glc).

The total chemical synthesis of lacto-N-tetraose (LNT) has been completed using both convergent and linear strategies. Similarly to that of our previous HMO syntheses, the donor-acceptor protecting-leaving group combinations were found to be of paramount significance to achieving successful glycosylations and minimizing side reactions.