Multicomponent Reactions in 11C/12C Chemistry: – Targeting the Angiotensin II Subtype 2 Receptor
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Section 1 of this thesis contains an introduction to method development in organic synthesis, multicomponent reactions, sulfonyl azides, tracer development in 11C chemistry and the biological target.
Section 2 describes the use of sulfonyl azides in carbonylative chemistry. Paper I covers development of a diazotransfer protocol. In total, 30 arylsulfonyl azides were synthesised from primary sulfonamides (20–90% yield). 15N mechanistic studies were carried out and in Paper II, the products were converted into sulfonamides, sulfonylureas and sulfonyl carbamates (19–90% yield). For ureas and carbamates, a two-chamber protocol was employed to release CO from Mo(CO)6. 15N mechanistic studies showed that the sulfonamides were formed by direct displacement of azide.
Section 3 covers imaging and biological studies of the angiotensin II receptor subtype 2 (AT2R). In Paper III, 12 11C-sulfonyl carbamates were prepared in isolated radiochemical yields of 3–51% via Rh(I)-mediated carbonylation. The first non-peptide AT2R agonist, C21, was labelled (isolated RCY 24±10%, SA 34–51 GBq/µmol). C21 was tested in a prostate cancer assay, followed by biodistribution and small-animal PET studies. In Paper IV, a 11C-labelled AT2R ligand prepared via Pd(0)-mediated aminocarbonylation was used for autoradiography, biodistribution and small-animal PET studies.
Section 4 describes the development of a multicomponent method for the synthesis of 3,4-dihydroquinazolinones (Paper V). 31 3,4-dihydroquinazolinones were synthesized via a cyclic iminium ion.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 93 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 219
carbonylation, positron emission tomography, multicomponent reactions, AT2R, 3, 4-dihydroquinazolinone, sulfonyl azides
Research subject Pharmaceutical Science
IdentifiersURN: urn:nbn:se:uu:diva-295436ISBN: 978-91-554-9636-4OAI: oai:DiVA.org:uu-295436DiVA: diva2:941172
2016-09-23, Hall B21, BMC, Husargatan 3, Uppsala, 09:15 (English)
Vasdev, Neil, Associate Professor
Odell, Luke, DocentLarhed, Mats, ProfessorAntoni, Gunnar, Adjunct ProfessorEstrada, Sergio, ForskareÅberg, Ola, Forskare
List of papers