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Catalytic and photochemical cycloadditions of alkynes
Fadeev, Aleksandr ; Kotora, Martin (advisor) ; Pour, Milan (referee) ; Parkan, Kamil (referee)
Novel approaches to utilizing alkynes in transition metal-catalyzed [2+2+2] cycloadditions and photochemical [2+2] cycloadditions were investigated with respect to the potential applications of these transformations. First, a chemo- and regioselective fully intermolecular cocyclotrimerization of internal alkynes with a commercially available ethynyl boronate was developed using Ru-catalysis and its mechanism was examined using DFT calculations. The established method allows for a straightforward preparation of various 1,4-diborylated benzenes, which can serve as multifunctional building blocks in organic synthesis. In particular, the products can be used in cross-coupling, carbonylation and oxidation reactions to access a broad variety of contiguously substituted arenes, such as natural products mirandamycin and violaceoid C. Second, a comparative study of catalytic and uncatalyzed photocycloadditions between alkynes and quinones was undertaken. Contrary to the recent reports, irradiation with visible light alone is sufficient to obtain not only the [2+2] cycloaddition products, but also several products of cascade transformations. Thus, depending on the structure of the quinone used, either carbo- or heterocycloaddition pathway is mainly realized, giving rise either to annulated cyclobutenes or...
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Preparation of novel types of acyclic nucleoside phosphonates for study of their interaction with enzymes of metabolism of nucleic acids
Kaiser, Martin Maxmilian ; Janeba, Zlatko (advisor) ; Jindřich, Jindřich (referee) ; Parkan, Kamil (referee)
This Ph.D. thesis is a part of detailed SAR studies among acyclic nucleoside phosphonates carried out in the group of the Nucleic acid chemistry (Prof. A. Holý) and later in the group of the Targeted analogues of nucleic acid components (Dr. Z. Janeba) at the IOCB AS CR, v.v.i. Three novel series of acyclic nucleoside phosphonates, namely carboxyphosphonomethoxyethyl (CPME), carboxyphos- phonoethoxyethyl (CPEE) and hydroxyphosphonoethoxypropyl (HPEP) derivatives were prepared in order to reveal their biological properties. The CPME compounds were designed as structural analogues of PMEA (9-[2- (phosphonomethoxy)ethyl]adenine, Adefovir) and (S)-HPMPA [(S)-9-(3-hydroxy-2- (phosphonomethoxy)propyl)adenine], well-known compounds with prominent antiviral effects. The key step in their synthesis was oxidation of primary hydroxyl group in HPMP precursors using TEMPO/sodium chlorite/sodium hypochlorite system. The initial docking studies indicated that (S)-CPMEA [(S)-3-(adenin-9-yl)-2- (phosphonomethoxy)propanoic acid)], 2'-carboxy analogue of PMEA, could be a candidate with promising anti-HIV activity. Although this compound did not show desired biological activity, its two prodrugs exhibited submicromolar anti-HCV activity. Prepared prodrugs of (S)-CPMEA were also shown to be weak inhibitors of adenylate...
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