Regioselective synthesis of curdlan derivatives

dc.contributor.authorZhang, Ruoranen
dc.contributor.committeechairEdgar, Kevin J.en
dc.contributor.committeememberWhittington, Abby R.en
dc.contributor.committeememberRoman, Marenen
dc.contributor.committeememberRiffle, Judy S.en
dc.contributor.committeememberTurner, S. Richarden
dc.contributor.departmentLearning Sciences and Technologiesen
dc.date.accessioned2015-12-26T09:05:29Zen
dc.date.available2015-12-26T09:05:29Zen
dc.date.issued2015-12-10en
dc.description.abstractCurdlan, a (1,3)-linked linear homopolysaccharide composed of beta-D-glucan, is produced by the bacterium Alcaligenes faecalis var. myxogenes. Several strategies to synthesize chemically modified curdlan derivatives have been reported, but there have been few reports of regioselective functionalization at specific positions of the curdlan backbone, especially of aminated curdlan derivatives which have remarkable potential in biomedical and pharmaceutical applications. We demonstrate herein the design, synthesis and characterization of a family of regioselectively aminated curdlan derivatives including 6-deoxy-6-(bromo/azido/amino/amido/ammonium) curdlans starting from 6-bromo/azido-6-deoxycurdlan. A key reaction that enabled the whole synthesis of new curdlan derivatives at C-6 described in this dissertation was the highly selective bromination of curdlan. The resultant 6-bromo-6-deoxycurdlan, prepared with high regioselectivity, was treated with trialkylamines or heterocyclic amines to produce a range of water-soluble curdlan ammonium salts. The bromide was then nucleophilically displaced by sodium azide to produce the versatile precursor 6-azido-6-deoxycurdlan. Its water solubility was enhanced either by the incorporation of hydrophilic trioxadecanoate esters into O-2/4 positions or by the borohydride reduction to afford 6-amino-6-deoxycurdlan. The iminophosphorane intermediate generated during Staudinger reactions was further investigated for subsequent syntheses: i) 6-amino or 6-amido-6-deoxycurdlan by in situ reaction with water or excess carboxylic anhydride, ii) 6-monoalkylamino curdlan by reductive amination using aldehydes and sodium cyanoborohydride, and iii) 6-dialkylamino-/tri-alkylammoniocurdlans by reacting with methyl iodide. Such derivatives could have properties useful for a range of biomedical applications, including interactions with proteins, encapsulation of drugs, and formulation with genes or other biological compounds.en
dc.description.degreePh. D.en
dc.format.mediumETDen
dc.identifier.othervt_gsexam:6673en
dc.identifier.urihttp://hdl.handle.net/10919/64374en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectcurdlanen
dc.subjectcurdlan derivativesen
dc.subjectregioselective synthesisen
dc.subjectamination at C-6en
dc.subjecttight junction openingen
dc.subjectwater-solubleen
dc.titleRegioselective synthesis of curdlan derivativesen
dc.typeDissertationen
thesis.degree.disciplineMacromolecular Science and Engineeringen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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