Synthesis of Hyaluronic Acid Oligomers using Chemoselective and One-Pot Strategies

Dinkelaar, Jasper; Gold, Henrik; Overkleeft, Herman S.; Codée, Jeroen D. C.; Marel, Gijsbert A. van der

doi:10.1021/jo9003713

Cited by 45 publications

(39 citation statements)

References 28 publications

(25 reference statements)

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“…While chemical syntheses of a variety of HA oligosaccharides have been accomplished [26–29], it is still very tedious to build up the oligosaccharide from the corresponding monosaccharide building blocks. To expedite the synthesis, we explored a new strategy, where a HA tetrasaccharide would be obtained through enzymatic digestion of HA polysaccharide and utilized for glyco-assembly.…”

Section: Resultsmentioning

confidence: 99%

Design and syntheses of hyaluronan oligosaccharide conjugates as inhibitors of CD44-Hyaluronan binding

Huang

2015

Glycoconj J

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Hyaluronan (HA) is an integral component of the extracellular matrix. Its interactions with a cell surface receptor CD44 has been shown to play important roles in a variety of biological events including cell proliferation and metastasis. As multivalent CD44-HA binding is critical for downstream signaling, compounds that can selectively disrupt the complex formation of HA polysaccharide with CD44 can serve as useful probes of CD44 mediated cellular events as well as potential leads for novel therapeutics. Herein, we report the synthesis of several series of HA conjugates to target the HA binding pocket of CD44. As a small library of HA disaccharide derivatives failed to exhibit any inhibitory activities, we focused on HA tetrasaccharide based analogs. Traditional synthetic strategies towards HA oligosaccharides involve the construction of backbone from the corresponding monosaccharide building blocks, which can be quite tedious. In order to expedite the synthesis, we designed a new synthetic route taking advantage of the ability of hyaluronidase to generate large quantities of HA tetrasaccharide through digestion of HA polysaccharides. The HA tetrasaccharide obtained was utilized to prepare multiple S-linked HA analogs bearing aromatic groups at the reducing end glycan. One such compound containing an m-benzyl phenyl moiety exhibited significant inhibition of CD44-HA binding. Our approach provides a new direction towards the design of HA based CD44 antagonists.

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Section: Resultsmentioning

confidence: 99%

Design and syntheses of hyaluronan oligosaccharide conjugates as inhibitors of CD44-Hyaluronan binding

Huang

2015

Glycoconj J

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“…For example, van der Marel and coworkers have reported the synthesis of the tri-, penta-, and heptamer of hyaluronic acid. [46] Huang and coworkers have reported the synthesis of a dodecamer of hyaluronic acid. [44, 47] Sleeman and Brase reported the multi-gram synthesis of a hyaluronic acid building block and a fully protected oligomer.…”

Section: Resultsmentioning

confidence: 99%

Regioselective Benzylation of 2‐Deoxy‐2‐aminosugars using Crown Ethers: Application to a Shortened Synthesis of Hyaluronic Acid Oligomers

2014

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The combination of benzyl bromide, sodium hydroxide and 15-crown-5 in tetrahydrofuran is shown to be an efficient method for installing benzyl groups at both the 4- and 6-positions regioselectively directly from peracetylated N-trichloroacetyl-protected glucosamine and galactosamine. Application of this benzylation strategy proved to significantly shorten the synthetic route to hyaluronic acid tetra- and hexamers.

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“…[37][38][39][40][41] Hyaluronic acid is a linear GAG featuring the β-(1Ǟ3)-linked, 2-acetamido-2-deoxy--glucose-β-(1Ǟ4)--glucuronic acid disaccharide as the repeating unit. [42][43][44] The synthesis of GAG oligosaccharide sequences is crucial for the establishment of specific structure-activity relationships in order to elucidate the role of these complex sugars in nature.…”

Section: Resultsmentioning

confidence: 99%

Polymer‐Supported Synthesis of Oligosaccharides Using a Diisopropylsiloxane Linker and Trichloroacetimidate Donors

2010

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We describe herein the polymer‐supported synthesis of biologically relevant oligosaccharides using a diisopropylsiloxane linker and trichloroacetimidates as glycosyl donors. Siloxane linkers offer important advantages over closely related silyl ethers since even sterically hindered alcohols can be directly loaded onto commercially available polymers, such as soluble polyethylene glycol (PEG), without prior manipulation of the support. Final products can be easily detached by mild fluoridolysis to afford OH‐tagged sugar probes. We followed an acceptor‐bound approach that fixed the nucleophile on the polymer, and we selected soluble PEG as the support due to higher reactivity of bound sugars and easy reaction monitoring. Following this strategy, the trisaccharide repeating unit of the capsular polysaccharide of Neisseria meningitidis (serogroup L) and the disaccharide containing the structural motif of hyaluronic acid were successfully synthesized.

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Synthesis of Hyaluronic Acid Oligomers using Chemoselective and One-Pot Strategies

Cited by 45 publications

References 28 publications

Design and syntheses of hyaluronan oligosaccharide conjugates as inhibitors of CD44-Hyaluronan binding

Design and syntheses of hyaluronan oligosaccharide conjugates as inhibitors of CD44-Hyaluronan binding

Regioselective Benzylation of 2‐Deoxy‐2‐aminosugars using Crown Ethers: Application to a Shortened Synthesis of Hyaluronic Acid Oligomers

Polymer‐Supported Synthesis of Oligosaccharides Using a Diisopropylsiloxane Linker and Trichloroacetimidate Donors

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