| 1. |
- Larsen, Anders Foller, 1984, et al.
(författare)
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Development of bright fluorescent quadracyclic adenine analogues: TDDFT-calculation supported rational design
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescent base analogues (FBAs) comprise a family of increasingly important molecules for the investigation of nucleic acid structure and dynamics. We recently reported the quantum chemical calculation supported development of four microenvironment sensitive analogues of the quadracyclic adenine (qA) scaffold, the qANs, with highly promising absorptive and fluorescence properties that were very well predicted by TDDFT calculations. Herein, we report on the efficient synthesis, experimental and theoretical characterization of nine novel quadracyclic adenine derivatives. The brightest derivative, 2-CNqA, displays a 13-fold increased brightness (epsilon Phi(F) = 4500) compared with the parent compound qA and has the additional benefit of being a virtually microenvironment-insensitive fluorophore, making it a suitable candidate for nucleic acid incorporation and use in quantitative FRET and anisotropy experiments. TDDFT calculations, conducted on the nine novel qAs a posteriori, successfully describe the relative fluorescence quantum yield and brightness of all qA derivatives. This observation suggests that the TDDFT-based rational design strategy may be employed for the development of bright fluorophores built up from a common scaffold to reduce the otherwise costly and time-consuming screening process usually required to obtain useful and bright FBAs.
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| 2. |
- Lawson, Christopher, 1968, et al.
(författare)
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Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescent base analogues (FBAs) have emerged as a powerful class of molecular reporters of location and environment for nucleic acids. In our overall mission to develop bright and useful FBAs for all natural nucleobases, herein we describe the synthesis and thorough characterization of bicyclic thymidine (bT), both as a monomer and when incorporated into DNA. We have developed a robust synthetic route for the preparation of the bT DNA monomer and the corresponding protected phosphoramidite for solid-phase DNA synthesis. The bT deoxyribonucleoside has a brightness value of 790 M(-1)cm(-1) in water, which is comparable or higher than most fluorescent thymine analogues reported. When incorporated into DNA, bT pairs selectively with adenine without perturbing the B-form structure, keeping the melting thermodynamics of the B-form duplex DNA virtually unchanged. As for most fluorescent base analogues, the emission of bT is reduced inside DNA (4.5- and 13-fold in single- and double-stranded DNA, respectively). Overall, these properties make bT an interesting thymine analogue for studying DNA and an excellent starting point for the development of brighter bT derivatives.
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| 3. |
- Bergh, Anders, et al.
(författare)
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Carbohydrate functionalization using cationic iron carbonyl complexes
- 2008
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Ingår i: Carbohydrate Research. - : Elsevier BV. - 1873-426X .- 0008-6215. ; 343:10-11, s. 1808-1813
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Tidskriftsartikel (refereegranskat)abstract
- Cationic iron carbonyl cyclohexadiene complexes were employed in the derivatization of the 3-OH position of unprotected and protected methyl beta-D-galactopyranosides using two different approaches, giving access to galactopyranosides with an aromatic or cyclohexadienoic functionality in this position. (c) 2008 Elsevier Ltd. All rights reserved.
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| 4. |
- Bromfield, Karen M., 1976, et al.
(författare)
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An iron carbonyl approach to the influenza neuraminidase inhibitor oseltamivir
- 2007
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1364-548X .- 1359-7345. ; :30, s. 3183-3185
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Tidskriftsartikel (refereegranskat)abstract
- A novel synthetic route towards oseltamivir, an influenza neuraminidase inhibitor, has been achieved employing a cationic iron carbonyl complex, providing an alternate pathway with the potential to access diverse analogues.
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| 5. |
- Bromfield, Karen M., 1976, et al.
(författare)
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Synthetic applications of cationic iron and cobalt carbonyl complexes
- 2009
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Ingår i: Dalton Transactions. - 1477-9226 .- 1477-9234. ; :26, s. 5051-5061
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Tidskriftsartikel (refereegranskat)abstract
- Metal carbonyl stabilized cationic species react with a wide range of nucleophiles under mild conditions, and have thus found many synthetic applications. In this Perspective, we describe the utility of iron carbonyl dienyl cations in solution and solid phase parallel synthesis, and in the development of a new synthetic route towards oseltamivir phosphate (Tamiflu). We also discuss the solid phase version of the Nicholas reaction, employing cobalt carbonyl stabilized propargylic cations, and giving access to substituted alkynes.
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| 6. |
- Eriksson, Jonas, et al.
(författare)
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Solid supported active esters as linkers: modification of reactivity using iron carbonyl complexes
- 2006
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Ingår i: Tetrahedron Letters. - : Elsevier BV. - 0040-4039 .- 1873-3581. ; 47:5, s. 635-638
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Tidskriftsartikel (refereegranskat)abstract
- The reactivity of three polymer-bound cyclohexadienoic acid active esters was modified by complexation with iron tricarbonyl in order to evaluate their potential use as linker systems for solid phase chemistry. The best results were obtained with the tetrallnorophenolester, which was slowly cleaved when 1 equiv of amine was used, but could be rapidly cleaved with up to 94% yield when the amount of nucleophile was increased. (c) 2005 Elsevier Ltd. All rights reserved.
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| 7. |
- Füchtbauer, Anders Foller, 1984, et al.
(författare)
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Lighting Up DNA with the Environment-Sensitive Bright Adenine Analogue qAN4
- 2020
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Ingår i: Chempluschem. - : Wiley. - 2192-6506. ; 85:2, s. 319-326
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Tidskriftsartikel (refereegranskat)abstract
- The fluorescent adenine analogue qAN4 was recently shown to possess promising photophysical properties, including a high brightness as a monomer. Here we report the synthesis of the phosphoramidite of qAN4 and its successful incorporation into DNA oligonucleotides using standard solid-phase synthesis. Circular dichroism and thermal melting studies indicate that the qAN4-modification has a stabilizing effect on the B-form of DNA. Moreover, qAN4 base-pairs selectively with thymine with mismatch penalties similar to those of mismatches of adenine. The low energy absorption band of qAN4 inside DNA has its peak around 358 nm and the emission in duplex DNA is partly quenched and blue-shifted (ca. 410 nm), compared to the monomeric form. The spectral properties of the fluorophore also show sensitivity to pH; a property that may find biological applications. Quantum yields in single-stranded DNA range from 1-29 % and in duplex DNA from 1-7 %. In combination with the absorptive properties, this gives an average brightness inside duplex DNA of 275 M-1 cm(-1), more than five times higher than the most used environment-sensitive fluorescent base analogue, 2-aminopurine. Finally, we show that qAN4 can be used to advantage as a donor for interbase FRET applications in combination with adenine analogue qA(nitro) as an acceptor.
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| 8. |
- Gradén, Henrik, 1968, et al.
(författare)
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Carbon-carbon and carbon-heteroatom bond formation on solid phase using cationic iron carbonyl complexes
- 2005
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Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7052 .- 1523-7060. ; 7:16, s. 3565-3567
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Tidskriftsartikel (refereegranskat)abstract
- Iron-mediated methodology for the formation of carbon-carbon and carbon-heteroatom sp(3) bonds on solid phase has been developed. Treatment of a polymer-bound cationic iron cyclohexadienyl complex with carbon, oxygen, nitrogen, and phosphorus nucleophiles, followed by cleavage with amines and subsequent decomplexation, yielded 18 different cyclohexadienoic acid amides of high purity.
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| 9. |
- Gradén, Henrik, 1968
(författare)
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Iron Carbonyl Mediated Parallel Synthesis
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes the examination and development of cationic iron carbonyl complexes for use in parallel synthesis both in solution phase and on solid phase. A solution phase methodology for carbon-carbon and carbon-heteroatom formation, utilizing polymer bound reagents and scavengers and amenable for automation has been successfully developed. Ten different nucleophiles (carbon, nitrogen, oxygen, and sulfur) were used, giving the targeted cyclohexadienoic amides in good yields and excellent purities. The solution phase methodology was transferred to a solid phase protocol, generating a diverse set of eighteen cyclohexadienoic amides of excellent purities and in good yields using nine different nucleophiles (carbon, nitrogen, oxygen, and phosphorous). Both methods use the same reaction conditions for all nucleophiles demonstrating the versatility of these methods in generating compound libraries of high diversity. Even sterically hindered nucleophiles like tert-butanol gave good results. Activated esters were also investigated as potential linkers for iron carbonyl mediated chemistry on solid phase, and a tetrafluorophenol linkage was found to be the most suitable for this purpose. Synthesis of oseltamivir analogues and galectin inhibitors based on cationic iron carbonyl chemistry has been undertaken and work is currently in progress to finalize these projects. This thesis also describes the investigation of a phosphate based linker for cationic iron carbonyl chemistry on solid phase. In solution phase, palladium and nickel catalyzed cross-coupling reaction cleaved the investigated enyl and dienyl phosphates to give the targeted olefins. However, when transferring to a solid phase protocol only traces of the desired olefin were detected. In summary, this thesis shows that cationic iron carbonyl chemistry is amenable for parallel synthesis both in solution and on solid phase using the same reaction conditions for a wide range of nucleophiles.Keywords: solid phase, parallel synthesis, scavenger, polymer bound reagent, iron carbonyl complex, cation, dienyl, active ester, linker, oseltamivir, galectin inhibitor
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| 10. |
- Gradén, Henrik, 1968, et al.
(författare)
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Solid phase synthesis using organometallic reagents
- 2005
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Ingår i: Current Organic Chemistry. - : Bentham Science Publishers Ltd.. - 1385-2728. ; 9:8, s. 733-763
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Tidskriftsartikel (refereegranskat)abstract
- The scope of organometallic reactions on solid phase has lately expanded to include many new reactions. In this review, we summarise the recent developments in this area, covering reactions such as metathesis, carbene insertion, radical-mediated transformations, the use of organomagnesium, organozinc and organocopper reagents, applications of titanium alkylidenes for alkene synthesis, as well as the Pauson-Khand reaction, hydroformylation and other methods using metal carbonyl reagents. Palladium-catalysed reactions are not included as this area has been recently reviewed (vide infra). © 2005 Bentham Science Publishers Ltd.
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