• Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of TUScholarShareCommunitiesDateAuthorsTitlesSubjectsGenresThis CollectionDateAuthorsTitlesSubjectsGenres

    My Account

    LoginRegister

    Help

    AboutPeoplePoliciesHelp for DepositorsData DepositFAQs

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Asymmetric Synthesis of Homotropinone and Tropane Alkaloids using Enantiopure Sulfinimines and the Synthesis and Applications of Methanoprolines

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Edupuganti_2011_155171.pdf
    Size:
    5.101Mb
    Format:
    PDF
    Download
    Genre
    Thesis/Dissertation
    Date
    2011
    Author
    Edupuganti, Ramakrishna
    Advisor
    Davis, Franklin A.
    Committee member
    Krow, Grant
    Andrade, Rodrigo B.
    Zdilla, Michael J., 1978-
    Cannon, Kevin C.
    Department
    Chemistry
    Subject
    Chemistry, Organic
    Chemistry
    Azabicycles
    Homotropinones
    Methanoprolines
    Methanopyrrolidines
    Sulfinimines
    Tropanes
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/1153
    
    Metadata
    Show full item record
    DOI
    http://dx.doi.org/10.34944/dspace/1135
    Abstract
    The development of new methodologies for the asymmetric synthesis of homotropinone and tropane alkaloids using enantiopure sulfinimines [RS(O)N=CR1R²] is the primary objective of this thesis. In one study a four-step intramolecular Mannich cyclization cascade reaction was devised for the asymmetric synthesis of substituted homotropinone alkaloids from enantiopure sulfinimine-derived N-sulfinyl ß-amino ketone ketals. These amino ketone ketal chiral building blocks were prepared in 67-71% yields and high dr (25-14:1) by addition of the Weinreb amide enolate of N-methoxy-Nmethylacetamide to masked oxo sulfinimines (N-sulfinyl imines). Treatment of these Weinreb amides with Grignard reagents gave the N-sulfinyl ß-amino ketone ketals in 93- 95% yields without epimerization. Heating the acyclic ß-amino ketone ketals with the buffer solution NH4OAc:HOAc resulted in a one-pot 4 step intramolecular Mannich cyclization cascade reaction to give substituted homotropinones including (–)- euphococcinine and (–)-adaline in 82-90% yields. In another study a sulfinimine-derived α,ß-unsaturated pyrrolidine nitrone was utilized in the development of a Lewis acid catalyzed [3+2] nitrone cycloaddition reaction for the asymmetric synthesis of the tropane alkaloid (+)-cocaine. The masked oxo sulfinimine was treated with an excess of the sodium enolate of methyl acetate to give N-sulfinyl ß-amino ester in 87% yield and high dr (97:3). Reduction of the ester to aldehyde followed by a Horner-Wadsworth-Emmons olefination reaction afforded the α,ß-unsaturated N-sulfinyl amino acetal. Hydrolysis of the unsaturated amino acetal gave a pyrrolidine, which was selectively oxidized to the pyrrolidine nitrone. The nitrone on heating with the Lewis acid Al(O-t-Bu)3 for 96 h underwent an intramolecular [3+2] cycloaddition to give a tricyclic isoxazolidine, which was transformed into (+)-cocaine in three steps 25% overall yield. This 9 step, 25% overall yield synthesis of (S)-(+)-cocaine from the masked oxo sulfinimine is the most efficient enantioselective route to cocaine from acyclic starting materials. This new methodology is adaptable to the preparation of various cocaine analogs including the first cocaine C-1 analogs. In other studies conformationally constrained novel pyrrolidine analogs (methanopyrrolidines) were synthesized stereoselectively to study the substituent (H, OH, or F) effect on amide conformational preferences. A nucleophilic displacement synthetic route was devised to prepare highly functionalized 5(6)-anti-substituted-methanopyrrolidines from N-benzyl-2-azabicyclo[2.1.1]hexylbromide(s) intermediates with the aid of neighboring group participation. These methanopyrrolidines were then transformed to constrained proline analogs (methanoprolines) to evaluate the impact of proline ring pucker on amide conformations. An α-methoxycarbonyl group was introduced in methanopyrrolidines by treating tert-butoxycarbonyl protected methanopyrrolidines with s-BuLi and quenching with various electrophiles such as CO2, DMF or ClCO2Me. Amide trans-cis conformational preferences (Ktrans/cis) of N-acetyl-methanopyrrolidines and N-acetyl-methanoprolines were determined in various solvents such as CDCl3 and D2O using NMR techniques, including NOE. The small trans amide preference for substituted fluoro- and hydroxy-methanopyrrolidines shows that it is the interaction of the !-methyl ester group and the amide moiety of the methanoprolines that plays a major role in determining amide conformational preferences. The gamma-substituent effect is primarily related to ring pucker and a resultant enhancement of the interaction between the amide carbonyl oxygen and ester carbonyl carbon. The results are relevant to the conformational stability of collagen and protein engineering.
    ADA compliance
    For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
    Collections
    Theses and Dissertations

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Temple University Libraries | 1900 N. 13th Street | Philadelphia, PA 19122
    (215) 204-8212 | scholarshare@temple.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.