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- Nilsson Lill, Sten O., 1970, et al.
(författare)
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tBu or not tBu?
- 2012
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539. ; 18:6, s. 1640-9
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Tidskriftsartikel (refereegranskat)abstract
- The regioselectivity in the palladium-catalyzed Heck coupling reaction between an aryl halide and ethyl vinyl ether with four different phosphine ligands: PPh(n)tBu(m) (n=0-3, m=3-n) has been investigated both experimentally and computationally. A zigzag selectivity pattern was experimentally observed upon consecutive replacement of Ph by tBu in the phosphine ligand. Use of a standard DFT method (B3LYP) was shown to give a correct prediction of product preference. However, the trend in relative selectivity among the different ligands could not be correctly described. The use of a more recent DFT functional (M06) parameterized to reproduce dispersion interactions resulted in an improved description. For the sterically most demanding ligands, PtBu(3) and PPhtBu(2), unexpectedly large deviations between experimental and M06 calculated selectivities raised the question of an alternative mechanism for these ligands. In the case of PtBu(3) it was found, in agreement with literature data, that the phosphine ligand could be replaced by a second halide ligand, resulting in an anionic mechanism, with a calculated selectivity in excellent agreement with experimental data. For the PPhtBu(2) ligand, two mechanisms are suggested to operate in parallel, as demonstrated both by computational studies and experimental observation of halide-dependent selectivity. A Halpern effect is observed for all phosphine ligands investigated, that is, the least stable pre-complex results in the most abundant product.
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| 2. |
- Ahlford, Katrin, et al.
(författare)
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Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Amino Acid Derived Rhodium Complexes : On the Origin of Enantioselectivity and Enantioswitchability
- 2009
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 15:42, s. 11197-11209
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Tidskriftsartikel (refereegranskat)abstract
- Amino acid based thioamides, hydroxamic acids, and hydrazides have been evaluated as ligands in the rhodium-catalyzed asymmetric transfer hydrogenation of ketones in 2-propanol. Catalysts containing thioamide ligands derived from L-valine were found to selectively generate the product with an R configuration (95 % ee), whereas the corresponding L-valine-based hydroxamic acids or hydrazides facilitated the formation of the (S)-alcohols (97 and 91 % ee, respectively). The catalytic reduction was examined by performing a structure–activity correlation investigation with differently functionalized or substituted ligands and the results obtained indicate that the major difference between the thioamide and hydroxamic acid based catalysts is the coordination mode of the ligands. Kinetic experiments were performed and the rate constants for the reduction reactions were determined by using rhodium–arene catalysts derived from amino acid thioamide and hydroxamic acid ligands. The data obtained show that the thioamide-based catalyst systems demonstrate a pseudo-first-order dependence on the substrate, whereas pseudo-zero-order dependence was observed for the hydroxamic acid containing catalysts. Furthermore, the kinetic experiments revealed that the rate-limiting steps of the two catalytic systems differ. From the data obtained in the structure–activity correlation investigation and along with the kinetic investigation it was concluded that the enantioswitchable nature of the catalysts studied originates from different ligand coordination, which affects the rate-limiting step of the catalytic reduction reaction.
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| 6. |
- Berndt, Vendela, et al.
(författare)
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The diagnostic value of salivary cortisol and salivary cortisone in patients with suspected hypercortisolism.
- 2022
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Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Diagnosing endogenous hypercortisolism remains a challenge, partly due to a lack of biochemical tests with good diagnostic accuracy.To evaluate the diagnostic value of salivary cortisol and cortisone in patients with suspected hypercortisolism.Retrospective study including 155 patients with adrenal incidentaloma, and 54 patients with suspected Cushing´s syndrome (CS). Salivary samples were collected at home, at 11 p.m., and at 8a.m. following an over-night dexamethasone suppression test (DST). Salivary cortisol and cortisone were measured with liquid chromatography-tandem mass spectrometry.Ten of 155 patients with adrenal incidentaloma were considered to have autonomous cortisol secretion (ACS). Using previously established cut-offs, all patients with ACS had elevated plasma-cortisol (>50 nmol/L) following DST, 9/10 had elevated late-night salivary cortisone (>15 nmol/L) whereas only 4/10 had elevated late-night salivary cortisol (LNSC; >3 nmol/L) compared to 35%, 9% and 8%, respectively, of the 145 patients with non-functioning adrenal incidentaloma. Six (60%) patents with ACS had elevated salivary cortisol and cortisone at 8a.m. following DST compared to 9% and 8%, respectively, of patients with non-functioning adrenal incidentaloma. One of 6 patients with overt CS had a normal LNSC and one had normal late-night salivary cortisone, while all had increased salivary cortisol and cortisone following DST.LNSC is not sufficiently sensitive or specific to be used for screening patients with suspected hypercortisolism. Instead, late-night salivary cortisone seems to be a promising alternative in patients with adrenal incidentaloma and salivary cortisone at 8a.m. following DST in patients with suspected CS. Larger studies are needed to confirm these findings.
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| 7. |
- Buitrago, Elina, et al.
(författare)
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High Throughput Screening of a Catalyst Library for the Asymmetric Transfer Hydrogenation of Heteroaromatic Ketones : Formal Syntheses of (R)-Fluoxetine and (S)-Duloxetine
- 2012
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Ingår i: ChemCatChem. - : Wiley. - 1867-3880 .- 1867-3899. ; 4:12, s. 2082-2089
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Tidskriftsartikel (refereegranskat)abstract
- A total of 21 amino acid based ligands including hydroxy amide, thioamide, and hydroxamic acid functionalities, respectively, were combined with [Ru(p-cymene)Cl2]2 and [RhCp*Cl2]2, and used as catalysts for the asymmetric transfer hydrogenation of four different heteroaromatic ketones in 2-propanol. The reactions were performed on a Chemspeed automated high-throughput screening robotic platform. Optimal catalysts were identified for the individual heterocyclic substrate classes. Based on these results, the formal syntheses of the antidepressant drugs (R)-fluoxetine and (S)-duloxetine were conducted by using the found catalysts in the key reaction step, which results in high isolated yields (94?%) and excellent product enantioselectivities (>99?% ee) of the formed 1,3-amino alcohols.
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| 8. |
- Buitrago, Elina, et al.
(författare)
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Selective reduction of heteroaromatic ketones: A combinatorial approach
- 2011
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The enantioselective reduction of prochiral ketones is a most productiveway towards enantio enriched secondary alcohols used in the preparation of biologically active compounds. There are numerous transition metal catalyzed methods for this transformation, particularly based on Ru(II)-and Rh(I)-complexes, but there is a demand for a larger substrate scope. Heteroaromatic ketones are traditionally more challenging substrates. Normally a catalyst is developed for one benchmark substrate, and asubstrate screen is made with the best performing catalyst. Using this methodology, there is a high probability that for different substrates, another catalyst could outperform the one used. We have executed a multiple screen, containing a variety of different ligands together with both Ru and Rh, and heteroaromatic ketones to fine-tune, and find the optimum catalyst depending on the substrate. The acquired information was used to synthesize known, biologically active compounds, where the key reduction steps were performed with high enantioselectivities and yields.
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| 9. |
- Dahlin, Mats, et al.
(författare)
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Internet-delivered acceptance-based behavior therapy for generalized anxiety disorder : A pilot study
- 2016
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 6, s. 16-21
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Internet-delivered cognitive behavior therapy (ICBT) has been developed and tested for treating persons with generalized anxiety disorder (GAD). A new form of CBT focuses on acceptance (of internal experiences or difficult psychological content), mindfulness and valued actions. To date this form of CBT has not been delivered via the internet for persons with GAD. The aim of this study was to describe the functionality of a new internet-delivered acceptance-based behavior therapy for GAD, and to test the effect of the intervention in an open pilot trial. Methods: Following exclusion of two patients we included 14 patients diagnosed with GAD from two primary care clinics. At 2–3 months follow-up after treatment 10 patients completed the outcome measures. The treatment lasted for an average of 15 weeks and consisted of acceptance-based techniques, behavior therapy components and homework assignments. Results: A majority of participants completed all modules during the treatment. Findings on the Penn State Worry Questionnaire showed a within-group improvement of Cohen's d = 2.14 at posttreatment. At the follow-up results were maintained. Client satisfaction ratings were high. Conclusions: We conclude that internet-delivered acceptance-based behavior therapy potentially can be a promising new treatment for GAD. A controlled trial of the program has already been completed.
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