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Enantioselective Synthesis of m-Carboranylalanine a Boron-rich Analogue of Phenylalanine
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
Article in journal (Refereed) Submitted
URN: urn:nbn:se:uu:diva-91770OAI: oai:DiVA.org:uu-91770DiVA: diva2:164609
Available from: 2004-04-22 Created: 2004-04-22Bibliographically approved
In thesis
1. Synthesis of Organic Compounds for Nuclide Therapy: Derivatives of Carboranes, 9-Aminoacridine and Anthracyclines
Open this publication in new window or tab >>Synthesis of Organic Compounds for Nuclide Therapy: Derivatives of Carboranes, 9-Aminoacridine and Anthracyclines
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis addresses the synthesis of organic compounds, some of them are derivatives of compounds with DNA binding properties, for potential use in targeted nuclide therapy. The compounds synthesized therefore also need to contain potent nuclides. Here the nuclides considered are the radionuclide 125I, and the stable isotope 10B, which becomes radioactive upon neutron activation. 125I is an Auger-electron emitter, which emits particles that can travel only about 1-2 µm through human tissue and hence has to be delivered to the cancer cell nucleus to cause DNA damage. Neutron activated 10B emits highly cell killing α-particles and 7Li3+ ions, the application of which in Boron Nuclide Capture Therapy (BNCT) has proven very promising.

The thesis can be divided into three parts:

i) A nido-carborate, 7-(3´-ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1), has been synthesized and radioiodinated for use as a pendant group for attachment of 125I to tumor-seeking macromolecules. Radiolabeling was achieved in greater than 95% yield.

ii) Both enantiomers of m-carboranylalanine, a carborane analogue of phenylalanine, have been prepared in high enantiomeric excess, and are of potential interest in BNCT. The synthesis involved amination of the N-acyl derivative formed from [3-(1,7-dicarba-closo-dodecarborane(12)-1-yl)-2-propanoic acid and Oppolzer’s camphor sultam.

iii) Derivatives of the DNA intercalating compounds 9-aminoacridine, daunorubicin and doxorubicin have been synthesized and labeled with 125I. The 9-aminoacridines were synthesised with a variety of functional groups such as carboxyl, amino and hydroxyl. The anthracylines daunorubicin and doxorubicin are efficient chemotherapeutic agents; the synthesis routes of ester, amide and amine derivatives of these compounds are presented.

The Chloramine T method was used for the radioiodinations, and the radioiodination precursors of both the acridine and the anthracycline derivatives, were made to contain either a trimethylstannyl group or a phenolic substituent. In the former case the trimethylstannyl group was replaced by 125I, and in the latter case, the compounds were radiolabeled directly at the o- position to the phenolic hydroxyl group. Both methods gave high radiolabeling yields.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 56 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 978
Organic chemistry, 9-Aminoacridin, Carborane, Daunorubicin, Doxorubicin, BNCT, Iodine-125, Organisk kemi
National Category
Organic Chemistry
urn:nbn:se:uu:diva-4264 (URN)91-554-5969-2 (ISBN)
Public defence
2004-05-14, Room B41, BMC, Husargatan 3, Uppsala, 13:15 (English)
Available from: 2004-04-22 Created: 2004-04-22 Last updated: 2011-04-14Bibliographically approved

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