| 1. |
- Engman, Mattias, 1979-
(författare)
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Chemo- and Enantioselective Hydrogenations : The Struggle of Expanding the Substrate Scope of Iridium Catalyzed Asymmetric Hydrogenations of Olefins
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The asymmetric hydrogenation of olefins is a facile and popular method of reaching chiral products. Whereas ruthenium- and rhodium-catalyzed asymmetric hydrogenations have a long history, the use of iridium in this area is new but fast-growing. Since the first chiral N,P-ligated iridium catalyst was created in the late 1990s, the growing pool of N,P ligands has filled up rapidly, but most have been tested with a limited range of standard olefins. To extract the full potential of these complexes, new methods using substrates having many possible applications must be developed. This thesis focuses on the iridium-catalyzed asymmetric hydrogenation of three different new substrate classes to yield very high conversions and enantiomeric excesses (ee's). As the use of fluorine has recently become common in many different fields of chemistry, the asymmetric reduction of fluoroolefins to reach chiral products having fluorine at the stereogenic centers is highly interesting. We studied this reaction and eventually obtained very high ee values and lower degree of defluorination (Paper I and Paper II). The hydrogenations of trifluoromethylated olefins to reach products useful in applications reaching from pharmaceuticals to additives in liquid crystal displays (LCDs) were also challenging, but fruitful (Paper III). As asymmetric hydrogenation usually demands differences in the substituents of the double bond, the highly selective reduction of 1,1-diaryl olefins having similar aryls give a new perspective on the broad scope of substrates that N,P-ligated iridium complexes can reduce selectively (paper IV).
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| 2. |
- Gogoll, Adolf, et al.
(författare)
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Alkylation and Convalent Adduct Formation of 2-Oxopurine
- 1993
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Ingår i: Heterocycles. - 0385-5414 .- 1881-0942. ; 36:2, s. 231-235
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Tidskriftsartikel (refereegranskat)abstract
- 2-Oxopurine reacted with benzyl bromide and ethanol to give the covalent adduct 1,3,7-tribenzyl-6-ethoxy-2-oxopurine, as well as dibenzylated products. Carbon-carbon bond formation was observed in the reaction between 2-oxopurine, dry silica gel, and benzyl bromide, giving rise to 6-hydroxy-1,3,8-tribenzyl-2-oxopurine.
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| 3. |
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| 4. |
- Proszenyák, Agnes, et al.
(författare)
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Synthesis, antimicrobial and antineoplastic activities for agelasine and agelasimine analogs with a beta-cyclocitral derived substituent.
- 2007
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Ingår i: Archiv der Pharmazie. - : Wiley. - 0365-6233 .- 1521-4184. ; 340:12, s. 625-634
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Tidskriftsartikel (refereegranskat)abstract
- Agelasines and agelasimines are antimicrobial and cytotoxic purine derivatives isolated from marine sponges (Agelas sp.). We have synthesized structurally simplified analogs of these natural products starting from beta-cyclocitral. The novel compounds were found to be strong inhibitors of a wide variety of pathogenic microorganisms (incl. Mycobacterium tuberculosis) as well as cancer cell lines. The biological activities were generally in the same range as those previously found for the structurally more complex agelasines and agelasimines isolated in small amounts from natural sources. We also report for the first time that agelasine and agelasimine analogs inhibit growth of protozoa (Acanthamoeba castellanii and Acanthamoeba polyphaga). Acanthamoeba keratitis is an increasingly common and severe corneal infection, closely associated with contact lens wear.
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| 5. |
- Roggen, Heidi, et al.
(författare)
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2-Substituted agelasine analogs : Synthesis and biological activity, and structure and reactivity of synthetic intermediates
- 2011
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Ingår i: Pure and Applied Chemistry. - 0033-4545 .- 1365-3075. ; 83:3, s. 645-653
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Tidskriftsartikel (refereegranskat)abstract
- 2-Substituted N-methoxy-9-methyl-9H-purin-6-amines were synthesized either from their corresponding 6-chloro-9-methyl-9H-purines or 2-chloro-N-methoxy-9-methyl-9H-purin-6-amine. Great diversity in the amino/imino tautomeric ratios was observed and calculated based on H-1 NMR. The tautomers were identified by 1D and 2D H-1, C-13, and N-15 NMR techniques, and showed significant variation both in C-13 and N-15 shift values. Comparison of the tautomeric ratios with Hammett F values revealed that as the field/inductive withdrawing abilities of the 2-substituent increased, the ratio of amino: imino tautomers was shifted toward the amino tautomer. Computational chemistry exposed the significance of hydrogen bonding between solvent and the compound in question to reach accurate predictions for tautomeric ratios. B3LYP/def2-TZVP density functional theory (DFT) calculations resulted in quantitatively more accurate predictions than when employing the less expensive BP86 functional. N-7-Alkylation of the 2-substituted N-methoxy-9-methyl-9H-purin-6-amines showed that when the field/inductive withdrawing ability of the 2-substituent reached a certain point the reactivity drastically dropped. This correlated with the atomic charges on N-7 calculated using a natural bond orbital (NBO) analysis. Biological screening of the final 2-substituted agelasine analogs indicated that the introduction of a methyl group in the 2-position is advantageous for antimycobacterial and antiprotozoal activity, and that an amino function may improve activity against several cancer cell lines.
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| 6. |
- Roggen, Heidi, et al.
(författare)
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Antimicrobial and antineoplastic activities of Agelasine analogs modified in the purine 2-position
- 2011
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Ingår i: Archiv der Pharmazie. - : Wiley. - 0365-6233 .- 1521-4184. ; 344:1, s. 50-55
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Tidskriftsartikel (refereegranskat)abstract
- Agelasines are 7,9-dialkylpurinium salts found in marine sponges (Agelas sp.), which display a variety of antimicrobial and cytotoxic effects. We have synthesized simplified agelasine analogs modified in the purine 2-position and examined their antimicrobial and anticancer activities. The compounds were screened against Staphylococcus aureus, Escherichia coli, Mycobacterium tuberculosis, Candida krusei, and Candida albicans, protozoa causing tropical diseases (Plasmodium falciparum, Leishmania infantum, Trypanosoma cruzi, and Trypanosoma brucei), a panel of human cancer cell lines (U-937 GTB, RPMI 8226/s, CEM/s, and ACHN) as well as VERO and/or MRC-5 cells. The results indicate that the introduction of a methyl group in the purine 2-position is beneficial for antimycobacterial and antiprotozoal activity, and that amino groups may enhance activity against several cancer cell lines.
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| 7. |
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| 8. |
- Vik, Anders, et al.
(författare)
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Antimicrobial and cytotoxic activity of agelasine and agelasimine analogs
- 2007
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 15:12, s. 4016-4037
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Tidskriftsartikel (refereegranskat)abstract
- Agelasine and agelasimine derivatives with substantially less complicated terpenoid side chains compared to the naturally occurring compounds have been synthesized and their ability to inhibit growth of microorganisms and cancer cells has been studied. Compounds with excellent activity against cancer cell lines (MIC ca. 1 μM for the most potent compounds), including a drug resistant renal cell line, have been identified. Most compounds studied also exhibited broad spectrum antimicrobial activity including activity against Mycobacterium tuberculosis.
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| 9. |
- Åkerbladh, Linda
(författare)
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Palladium(0)-Catalysed Carbonylative Multicomponent Reactions : Synthesis of Heterocycles and the Application of Quinolinyl Pyrimidines as Enzyme Inhibitors
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Palladium-catalysed carbonylative multicomponent reactions have proven useful for the synthesis of structurally diverse compounds. Carbon monoxide serves as an atom-efficient, one-carbon building block, which allows for further structural elaboration of the carbonyl compound. By varying the components of the carbonylative multicomponent reaction, considerable product diversity can readily be attained. However, due to the reluctance to use toxic CO gas, considerable efforts have been directed at exploring non-gaseous approaches. The work described in this thesis has mainly focused on the development of palladium(0)-catalysed, carbonylative multicomponent synthetic methodology, using the non-gaseous CO source molybdenum hexacarbonyl, in the synthesis of heterocycles and other biologically relevant functional groups.The first part of this work describes the development of a non-gaseous carbonylative Sonogashira cross-coupling of bifunctional ortho-iodoanilines and terminal alkynes. Where 4-quinolones were synthesised via a carbonylation/cyclisation sequence. Using a similar synthetic strategy, three different N-cyanobenzamide intermediates were prepared by palladium-catalysed carbonylative couplings of various aryl halides and bromides and cyanamide. The formed intermediates provided a basis for further chemical transformations. First, ortho-iodoanilines were carbonylatively coupled with cyanamide and subsequently cyclised to yield heterocyclic 2-aminoquinazolinones. Next, building on those findings, the same synthetic strategy was applied to ortho-halophenols to provide a highly convenient domino carbonylation/cyclisation method for the preparation of benzoxazinones. The developed method was used to evaluate the efficiency of various non-gaseous CO sources. Third, the palladium-catalysed carbonylative synthesis of N-cyanobenzamides, was used to produce biologically relevant N-acylguanidines with considerable product diversity. Finally, one of the developed carbonylative methodologies was used in the preparation of potential NDH-2 inhibitors based on a quinolinyl pyrimidine scaffold. The prepared compounds were biologically evaluated in terms of inhibition of oxidoreductase NDH-2 and antibacterial activity on Gram-negative bacteria, S. aureus and Mtb. The biological evaluation revealed that some of the quinolinyl pyrimidines exerted inhibitory activity on the NDH-2 enzyme and possessed antibacterial properties.The work described in this thesis has been devoted to the development of non-gaseous one-pot, multicomponent carbonylation/cyclisation and carbonylation/amination reactions. The described methods offer highly attractive synthetic strategies that can be of great value to synthetic and medicinal chemists.
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