KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Pharmaceutical Chemistry
    • Pharmaceutical Chemistry Scholarly Works
    • View Item
    •   KU ScholarWorks
    • Pharmaceutical Chemistry
    • Pharmaceutical Chemistry Scholarly Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Mechanism of Autoxidation of 5, 7-Dihydroxytryptamine : Effect of Fluorine Substitution at Positions 4 and /or 6

    Thumbnail
    View/Open
    BorchardtR_CPB_38(11)2939.pdf (1.240Mb)
    Issue Date
    1990
    Author
    Kawase, Masami
    Shinababu, Achintya
    Borchardt, Ronald T.
    Publisher
    The Pharmaceutical Society of Japan
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Metadata
    Show full item record
    Abstract
    Analogs of 5, 7-dihydroxytryptamine (5, 7-DHT), namely, 4-fluoro-, 6-fluoro-, and 4, 6-difluoro-5, 7-DHT's (30a-c) were synthesized starting from 4-fluorophenol (7a), 4-fluorobenzyl alcohol (12) and 2, 4-difluorophenol (7b), erspectively.Regiospecific hydroxylation and formylation ortho to fluoro groups, both via aryllithium intermediates, were made possible by the blocking effect of tert-butyldimethylsilyloxy functions and allowed the conversion of the starting materials to the key intermediates, namely, 3, 5-bis(tert-butyldimethylsilyloxy)-2-fluoro-, 4-fluoro- and 2, 4-difluorobenzaldehydes (11a, b and 19, respectively). The latter were converted in one step to the corresponding benzyloxybenzaldehydes, from which indole-2-carboxylates 22a-c were synthesized via azidostyrenes 21a-c, respectively. Decarbonylation of the indole-2-carboxaldehydes(24a-c) produced from 22a-c in two steps gave 2, 3-unsubstituted indoles 25a-c, respectively.Introduction of the aminoethyl side chains on C-3 of 25a-c via the corresponding indole-3-acetonitriles, and subsequent debenzylation generated the hydroxytryptamines, which were isolated as their creatinine sulfate salts 30a-c, respectively.Cyclic voltammetric studies indicated that like 5, 7-DHT, 30a-c undergo electrochemical oxidation in 1M H2SO4 via the corresponding P-quinoneimine derivatives 31a-c by an electrochemical-chemical-electrochemical (ECE) process. The voltammetrically detectable products of the ECE process appear to be the corresponding 5-hydroxytryptamine-4, 7-dione (6) derivatives 33a-c. The nature of the interaction of dissolved O2 with 30a-c at pH 7.4 appears to be strikingly different from that of 5, 7-DHT, which undergoes autoxidation at pH 7.4 via the 4-hydroperoxy derivative 4 to the quinone 6. Thus, contrary to expectation and as judged by ultraviolet-visible spectroscopy, 30a undergoes autoxidation via the p-quinoneimine 31a to give the quinone 6 with loss of fluorine ion while 30b gives an unidentified colorless product(s) and 30c does not react with oxygen at pH 7.4.
    URI
    http://hdl.handle.net/1808/17748
    DOI
    https://doi.org/10.1248/cpb.38.2939
    Collections
    • Pharmaceutical Chemistry Scholarly Works [327]
    Citation
    Kawase, Masami, Achintya K. Sinhababu and Ronald T. Borchardt. "Mechanism of Autoxidation of 5, 7-Dihydroxytryptamine : Effect of Fluorine Substitution at Positions 4 and /or 6." Chemical and Pharmaceutical Bulletin Vol. 38 (1990) No. 11 P 2939-2946. http://doi.org/10.1248/cpb.38.2939

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps