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I. LEWIS BASE-CATALYZED ALDOL REACTION IN THE TOTAL SYNTHESIS OF ERYTHRONOLIDE B; II. EFFORTS TOWARDS THE TOTAL SYNTHESIS OF AMPHIDINOLIDE H

Fu, Dezhi (2011) I. LEWIS BASE-CATALYZED ALDOL REACTION IN THE TOTAL SYNTHESIS OF ERYTHRONOLIDE B; II. EFFORTS TOWARDS THE TOTAL SYNTHESIS OF AMPHIDINOLIDE H. Doctoral Dissertation, University of Pittsburgh.

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    Abstract

    Lewis base (trimethylsilylquinine and trimethylsilylquinidine) catalyzed acyl halide-aldehyde cyclocondensation (AAC) reactions have been developed to prepare synthetically important bispropionate units previously by the Nelson group. A new Lewis base-catalyzed diastereoselective Mukaiyama aldol reaction has extended this bispropionate unit preparation methodology to all-syn bispropionates which widely occurred in polypropionate natural products. By using phenoxides as Lewis base catalysts, enol silanes were activated and underwent a Felkin attack on an aldehyde through an antiperiplanar transition state to generate all-syn bispropionate product in high yields and excellent diastereoselectivities.All-syn bispropionate prepared from the Lewis base-catalyzed diastereoselective Mukaiyama aldol reaction has been untilized in natural product synthesis of erythronolide B establishing ¡°syn,syn,syn¡± stereochemical relationships from C2-C5.Studies towards the total synthesis of the cytotoxic marine macrolide amphidinolide H have been disclosed. By exploiting AAC methodology, several key stereochemical relationships present in major fragments 198 and 199 were established. A highly enantioselective synthesis of methyl ketone 200 was realized from commercially available (S)-(−)-glycidol. Iodide 198 was coupled with boronic ester 199 via an efficient Suzuki reaction to form a C7-C20 fragment.

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    Details

    Item Type: University of Pittsburgh ETD
    ETD Committee:
    ETD Committee TypeCommittee MemberEmail
    Committee ChairNelson, Scott Gsgnelson@pitt.edu
    Committee MemberDay, Billy Wbday@pitt.edu
    Committee MemberWilcox, Craig Sdaylite@pitt.edu
    Committee MemberCohen, Theodorecohen@pitt.edu
    Title: I. LEWIS BASE-CATALYZED ALDOL REACTION IN THE TOTAL SYNTHESIS OF ERYTHRONOLIDE B; II. EFFORTS TOWARDS THE TOTAL SYNTHESIS OF AMPHIDINOLIDE H
    Status: Unpublished
    Abstract: Lewis base (trimethylsilylquinine and trimethylsilylquinidine) catalyzed acyl halide-aldehyde cyclocondensation (AAC) reactions have been developed to prepare synthetically important bispropionate units previously by the Nelson group. A new Lewis base-catalyzed diastereoselective Mukaiyama aldol reaction has extended this bispropionate unit preparation methodology to all-syn bispropionates which widely occurred in polypropionate natural products. By using phenoxides as Lewis base catalysts, enol silanes were activated and underwent a Felkin attack on an aldehyde through an antiperiplanar transition state to generate all-syn bispropionate product in high yields and excellent diastereoselectivities.All-syn bispropionate prepared from the Lewis base-catalyzed diastereoselective Mukaiyama aldol reaction has been untilized in natural product synthesis of erythronolide B establishing ¡°syn,syn,syn¡± stereochemical relationships from C2-C5.Studies towards the total synthesis of the cytotoxic marine macrolide amphidinolide H have been disclosed. By exploiting AAC methodology, several key stereochemical relationships present in major fragments 198 and 199 were established. A highly enantioselective synthesis of methyl ketone 200 was realized from commercially available (S)-(−)-glycidol. Iodide 198 was coupled with boronic ester 199 via an efficient Suzuki reaction to form a C7-C20 fragment.
    Date: 22 June 2011
    Date Type: Completion
    Defense Date: 08 April 2011
    Approval Date: 22 June 2011
    Submission Date: 15 April 2011
    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-04152011-183517
    Uncontrolled Keywords: AAC; Amphidinolide H; Erythronolide B; Lewis Base; Macrolides; Mukaiyama Aldol; Ployketide
    Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
    Date Deposited: 10 Nov 2011 14:37
    Last Modified: 08 May 2012 09:30
    Other ID: http://etd.library.pitt.edu/ETD/available/etd-04152011-183517/, etd-04152011-183517

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