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OLIGOMERIC ETHYLENE GLYCOLS AS SORTING TAGS FOR COMBINATORIAL SYNTHESIS

Türkyilmaz, Serhan (2007) OLIGOMERIC ETHYLENE GLYCOLS AS SORTING TAGS FOR COMBINATORIAL SYNTHESIS. Doctoral Dissertation, University of Pittsburgh.

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    Abstract

    Certain problems associated with the nature of solid phase combinatorial synthesis has prompted the search for alternative methods. Among these, fluorous mixture synthesis (FMS) has emerged as a powerful method for solution phase combinatorial synthesis. In FMS each unique substrate is tagged with a perfluorinated alkane of unique length. These tagged substrates are mixed and taken through the desired synthetic steps. The final products are then subjected to fluorous chromatography. Elution order is directly proportional to fluorous tag length. Thus such fluorous tags could be regarded as sorting tags. Other classes of sorting tags which are separable under orthogonal conditions to those of fluorous tags would significantly increase the potential of this approach. In this study it has been demonstrated that oligomeric ethylene glycol (OEG) derivatives constitute a new class of sorting tags. OEG esters were separable using normal phase high performance liquid chromatography (NPLC). Separation was primarily dictated by OEG chain length with elution order being directly proportional to that length. Within those separatory regions the nature of the parent substrate played a secondary role, further improving separation. It has also been demonstrated that complexation chromatography employing silica gel containing lithium chloride further enhanced peak resolution. OEGylated analogues of benzyl alcohol have been prepared. Reversed phase high performance liquid chromatography has been found to emphasize the chromatographic nature of the parent substrate while still enabling OEG based separation. The elution order with respect to OEG chain length was found to be the opposite of that in NPLC. Enthalpy-entropy compensation has been demonstrated for all OEG chain lengths indicating the same retention mechanism for all of the esters studied. These findings suggest that a two-tier separation approach-first RPLC then NPLC-could significantly increase the number of OEGylated substrates that can be subjected to mixture synthesis. OEGylated Evans Auxiliaries (OEG-EAs) have been prepared and applied to mixture syn-aldol reactions to demonstrate the synthetic utility of OEG-based sorting tags. OEGs have been found to be inert under the reaction conditions employed in the preparation of and application of OEG-EAs. The aldol products were obtained with good yield, high purity and high enantiomeric excess.


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    Item Type: University of Pittsburgh ETD
    ETD Committee:
    ETD Committee TypeCommittee MemberEmail
    Committee ChairWilcox, Craig Sdaylite@pitt.edu
    Committee MemberCurran, Dennis Pcurran@pitt.edu
    Committee MemberBeckman, Eric Jbeckman@engr.pitt.edu
    Committee MemberChapman, Toby Mtchapman@pitt.edu
    Title: OLIGOMERIC ETHYLENE GLYCOLS AS SORTING TAGS FOR COMBINATORIAL SYNTHESIS
    Status: Unpublished
    Abstract: Certain problems associated with the nature of solid phase combinatorial synthesis has prompted the search for alternative methods. Among these, fluorous mixture synthesis (FMS) has emerged as a powerful method for solution phase combinatorial synthesis. In FMS each unique substrate is tagged with a perfluorinated alkane of unique length. These tagged substrates are mixed and taken through the desired synthetic steps. The final products are then subjected to fluorous chromatography. Elution order is directly proportional to fluorous tag length. Thus such fluorous tags could be regarded as sorting tags. Other classes of sorting tags which are separable under orthogonal conditions to those of fluorous tags would significantly increase the potential of this approach. In this study it has been demonstrated that oligomeric ethylene glycol (OEG) derivatives constitute a new class of sorting tags. OEG esters were separable using normal phase high performance liquid chromatography (NPLC). Separation was primarily dictated by OEG chain length with elution order being directly proportional to that length. Within those separatory regions the nature of the parent substrate played a secondary role, further improving separation. It has also been demonstrated that complexation chromatography employing silica gel containing lithium chloride further enhanced peak resolution. OEGylated analogues of benzyl alcohol have been prepared. Reversed phase high performance liquid chromatography has been found to emphasize the chromatographic nature of the parent substrate while still enabling OEG based separation. The elution order with respect to OEG chain length was found to be the opposite of that in NPLC. Enthalpy-entropy compensation has been demonstrated for all OEG chain lengths indicating the same retention mechanism for all of the esters studied. These findings suggest that a two-tier separation approach-first RPLC then NPLC-could significantly increase the number of OEGylated substrates that can be subjected to mixture synthesis. OEGylated Evans Auxiliaries (OEG-EAs) have been prepared and applied to mixture syn-aldol reactions to demonstrate the synthetic utility of OEG-based sorting tags. OEGs have been found to be inert under the reaction conditions employed in the preparation of and application of OEG-EAs. The aldol products were obtained with good yield, high purity and high enantiomeric excess.
    Date: 27 September 2007
    Date Type: Completion
    Defense Date: 13 July 2007
    Approval Date: 27 September 2007
    Submission Date: 31 July 2007
    Access Restriction: No restriction; Release the ETD for access worldwide immediately.
    Patent pending: No
    Institution: University of Pittsburgh
    Thesis Type: Doctoral Dissertation
    Refereed: Yes
    Degree: PhD - Doctor of Philosophy
    URN: etd-07312007-043012
    Uncontrolled Keywords: complexation chromatography; Evans Auxiliary; fluorous mixture synthesis; HPLC; normal phase; protecting group; reversed phase; syn-aldol reaction
    Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
    Date Deposited: 10 Nov 2011 14:55
    Last Modified: 02 Jul 2013 13:54
    Other ID: http://etd.library.pitt.edu/ETD/available/etd-07312007-043012/, etd-07312007-043012

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