From Polymer to Size‐Defined Oligomers: A Highly Divergent and Stereocontrolled Construction of Chondroitin Sulfate A, C, D, E, K, L, and M Oligomers from a Single Precursor: Part 2

Abstract

An efficient, stereocontrolled, and highly divergent approach for the preparation of oligomers of chondroitin sulfate (CS) A, C, D, E, K, L, and M variants, starting from a single precursor easily obtained by semisynthesis from abundant natural polymer is reported for the first time. Common intermediates were designed that allowed the straightforward construction of O-sulfonated species either on the D-galactosamine unit (CS-A, -C, and -E) or on both D-glucuronic acid and D-galactosamine units (CS-D and CS-K, -L, and -M). This strategy represents a successful improvement and brings a definitive answer toward the synthesis of such complex molecules with numerous relevant biological functions.

Synthesis of a chondroitin sulfate disaccharide library and a GAG-binding protein interaction analysis

“…Although the synthesis of CS oligosaccharides has been studied extensively, [8][9][10][11][12][13][14][15][16][17][18] the design and synthesis of the building blocks for generating a CS library is still challenging. In the present study, to exhaustively investigate the binding properties of proteins or viruses at the molecular level, we demonstrated the systematic synthesis of all 16 kinds of CS partial disaccharide structures possessing a diverse sulfation set.…”

Effect of Nonanimal High- and Low-Molecular-Mass Chondroitin Sulfates Produced by a Biotechnological Process in an Animal Model of Polyarthritis

“…In order to overcome the abovementioned drawbacks, several chemical/biotechnological approaches have been developed to produce CS of nonextractive origin, having structures and properties similar to the animal polysaccharide [11,12,13,14]. However, to date, no biological activity has ever been tested and confirmed for these nonextractive polysaccharides.…”

Efficient and Stereocontrolled Construction of Homo‐ and Heterogeneously 4‐ and 6‐Sulfated Biotinylated Chondroitin Oligomers

“…To avoid tedious protection-deprotection steps for the preparation of key intermediates 3 and 4, in which hydroxy groups were further O-sulfonated, we applied a one-pot process similar to those still reported for the preparation of CS -K and L oligomers. [9] Diol 2 was thus treated with trimethyl orthobenzoate and a catalytic amount of CSA in dichloromethane to give the intermediate 4,6-orthoester, which upon mild acid hydrolysis afforded the 6-O-benzoyl (3) and the 4-O-benzoyl (4) derivatives in a 1:1 ratio and in excellent yield. Radical reduction [10] of 3 and 4 with tri-n-butylstannane afforded smoothly the acetamides 5 (79 %) and 6 (88 %), respectively, which were further treated with sulfur trioxide/trimethylamine complex in N,N-dimethylformamide (DMF) to provide, after ion exchange with a [Na + ] resin, the sulfated derivatives 7 (92 %) and 8 (82 %), respectively.…”

“…[9] Within a program devoted to the study of the biosynthetic pathways of CS chains in relation to osteoarthritis, we report herein an efficient and stereocontrolled construction of homo-and heterogeneously 4-and 6-sulfated chondroitin oligomers as their biotinylated conjugates, which are useful molecules as probes for studying the initiation of the polymerization of CS chains and the role of sulfotransferases involved in CS chain construction in cartilage.…”

“…Part 2: Ref. [9] [a] tions; these should be useful probes for the study of the starting point of the polymerization reaction as well as the substrate specificity of sulfotransferases involved in the biosynthesis of chondroitin sulfate chains.…”