Threshold of Thioglycoside Reactivity Difference Is Critical for Efficient Synthesis of Type I Oligosaccharides by Chemoselective Glycosylation.

Synthesis of type I LacNAc (Galß1 → 3GlcNAc) oligosaccharides usually suffers from low yields. We herein report the efficient synthesis of type I LacNAc oligosaccharides by chemoselective glycosylation. With 16 relative reactivity values (RRVs) measured thiotoluenyl-linked disaccharide donors and acceptors, chemoselective glycosylations were investigated to obtain optimal conditions. In these reactions, the RRV difference between the donors and acceptors had to be more than 6311 to obtain type I LacNAc tetrasaccharides in 72-86% yields, with minimal occurrence of aglycon transfer. The threshold of RRV difference was further applied to plan the synthesis of longer glycans. Because it is challenging to measure the RRVs of tetrasaccharides, anomeric proton chemical shifts were utilized to predict the corresponding RRVs, which consequently explained the outcome of glycosylations for the synthesis of type I LacNAc hexasaccharides. The result supported the idea that elongation of glycan chains has to proceed from the reducing to the nonreducing end for a better yield.

Synthesis of Type-I and Type-II LacNAc-Repeating Oligosaccharides as the Backbones of Tumor-Associated Lewis Antigens.

Type-I and Type-II LacNAc are Gal-GlcNAc disaccharides bearing a ß1,3- or ß1,4-linkage respectively. They exist as the backbones of Lewis antigens that are highly expressed in several cancers. Owing to the promise of developing carbohydrate-based anti-cancer vaccines, glycan synthesis at a large scale is indeed an important task. Synthesis of Type-I and Type-II tandem repeat oligomers has been hampered by the presence of GlcNAc residues. Particularly, N-protecting group plays a determining role in affecting glycosyl donor's reactivity and acceptor's nucleophilicity. This review discusses several representative studies that assembled desirable glycans in an efficient manner, such as chemoselective one-pot synthesis and chemoenzymatic methods. Additionally, we also highlight solutions that have been offered to tackle long-lasting problems, e.g., prevention of the oxazoline formation and change of donor/acceptor reactivity. In retrospect of scientific achievements, we present the current restrictions and remaining challenges in this less explored frontier.

Fluorescent Sensing of Guanine and Guanosine Monophosphate with Conjugated Receptors Incorporating Aniline and Naphthyridine Moieties.

Ethyne-linked naphthyridine-aniline conjugated molecules are selective sensors of decylguanine in dichloromethane and guanosine monophosphate in water (Kass = 16,000 M(-1)). The 2-acetamido-1,8-naphthyridine moiety binds with guanine in a DAA-ADD triply hydrogen-bonded motif. The aniline moiety enhances an electron-donating effect, and the substituent is tuned to attain extra hydrogen bonds, π-π stacking, and electrostatic interactions. The proposed binding modes are supported by a Job plot, ESI-MS, (1)H NMR, UV-vis, and fluorescence spectral analyses.