Title page for ETD etd-11152011-121453

Type of Document Dissertation
Author Fox, Stephen Carter
URN etd-11152011-121453
Title Regioselective Synthesis of Novel Cellulose Derivatives for Drug Delivery
Degree PhD
Department Macromolecular and Science Engineering
Advisory Committee
Advisor Name Title
Edgar, Kevin J. Committee Chair
Frazier, Charles E. Committee Member
Hanson, Brian E. Committee Member
Long, Timothy E. Committee Member
Roman, Maren Committee Member
  • drug delivery
  • Staudinger reduction
  • cellulose
  • regioselective synthesis
  • cellulose derivatives
Date of Defense 2011-11-04
Availability unrestricted
New methods were developed for the regioselective synthesis of new classes of cellulose derivatives with properties that could help improve the delivery of pharmaceutical drugs within the human body. The specific synthetic targets of this research were regioselectively carboxylated and regioselectively aminated cellulose derivatives. While different avenues to the carboxylated cellulose were ultimately explored without success, a new method for the synthesis of selectively O-acylated 6-amino-6-deoxy-cellulose esters was devised.

A key reaction that enabled the synthesis of the new cellulose derivatives described in this dissertation was the one-pot conversion of microcrystalline cellulose to 6-bromo-6-deoxy-cellulose esters. This reaction resulted in the highly selective displacement of the primary hydroxyl groups attached to the 6-carbon (C-6) on each anhydroglucose unit (AGU) in cellulose with bromide, with little or no bromination occurring at carbons 2 and 3 (C-2 and C-3). The brominated cellulose was then completely esterified by adding acetic, propionoic, or butyric acid anhydride to the reaction solution. The reaction products were readily soluble in many common organic solvents, including acetone, dimethyl sulfoxide, dimethylformamide, tetrahydrofuran, and chloroform. It was shown that the bromides could be converted to iodides under Finkelstein reaction conditions.

The presence of halides at C-6 allows a variety of new functional groups to be regioselectively introduced to cellulose via nucleophilic substitution. In one case, the 6-bromo-6-deoxy-cellulose esters were reacted with sodium cyanide to produce regioselectively synthesized cellulose nitriles. These compounds were synthesized with the idea that they could be converted to regioselectively carboxylated cellulose derivatives as an alternative pathway to the rhodium-catalyzed carbonyl insertion reactions also attempted in this research. However, the cellulose nitriles were highly susceptible to alkaline degradation, and conversion to the carboxylated cellulose was not achieved.

The 6-bromo-6-deoxy-cellulose esters were also reacted with sodium azide to successfully produce 6-azido-6-deoxy-cellulose esters. The azide groups were then reduced to amines using the Staudinger reaction. This very mild and selective reaction allowed the conversion of the azides to amines in the presence of the ester groups still attached to the cellulose backbone. Such derivatives could have properties useful for a range of biomedical applications, including the delivery of anionic drugs.

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