| 1. |
- Andersson, Hans, et al.
(författare)
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Complete regioselective addition of grignard reagents to pyrazine N-oxides, toward an efficient enantioselective synthesis of substituted piperazines.
- 2010
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Ingår i: Organic letters. - : American Chemical Society (ACS). - 1523-7052 .- 1523-7060. ; 12:2, s. 284-6
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Tidskriftsartikel (refereegranskat)abstract
- A conceptually new one-pot strategy for the synthesis of protected substituted piperazines via the addition of Grignard reagents to pyrazine N-oxides is presented. This strategy is high yielding (33-91% over three steps), step-efficient, and fast. The synthesized N,N-diprotected piperazines are convenient to handle and allow for orthogonal deprotection at either nitrogen for selective transformations. In addition, this is a synthetic route to enantiomerically enriched piperazines by using a combination of phenyl magnesium chloride and (-)-sparteine, which resulted in enantiomeric excesses up to 83%.
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| 2. |
- Andersson, Hans, et al.
(författare)
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Efficient, mild and completely regioselective synthesis of substituted pyridines
- 2010
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Ingår i: Chemical Communications. - : RSC Publishing. - 1359-7345 .- 1364-548X. ; 46:19, s. 3384-3386
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Tidskriftsartikel (refereegranskat)abstract
- Addition of Grignard reagents to pyridine N-oxides in THF at low temperature (-78 to -20 °C) and treatment with TFAA provides an efficient general procedure for synthesis of substituted pyridines. The method is compatible with a range of functional groups such as esters, halogens and nitriles.
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| 3. |
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| 4. |
- Chorell, Erik, et al.
(författare)
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Mapping pilicide anti-virulence effect in Escherichia coli, a comprehensive structure-activity study
- 2012
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier. - 0968-0896 .- 1464-3391. ; 20:9, s. 3128-3142
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Tidskriftsartikel (refereegranskat)abstract
- Pilicides prevent pili formation and thereby the development of bacterial biofilms in Escherichia coli. We have performed a comprehensive structure activity relationship (SAR) study of the dihydrothiazolo ring-fused 2-pyridone pilicide central fragment by varying all open positions. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to distinguish active from inactive compounds in which polarity proved to be the most important factor for discrimination. A quantitative SAR (QSAR) partial least squares (PLS) model was calculated on the active compounds for prediction of biofilm inhibition activity. In this model, compounds with high inhibitory activity were generally larger, more lipophilic, more flexible and had a lower HOMO. Overall, this resulted in both highly valuable SAR information and potent inhibitors of type 1 pili dependent biofilm formation. The most potent biofilm inhibitor had an EC(50) of 400nM.
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| 5. |
- Chorell, Erik, et al.
(författare)
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Synthesis and application of a bromomethyl substituted scaffold to be used for efficient optimization of anti-virulence activity
- 2011
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier Masson SAS. - 0223-5234 .- 1768-3254. ; 46:4, s. 1103-1116
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Tidskriftsartikel (refereegranskat)abstract
- Pilicides are a class of compounds that attenuate virulence in Gram negative bacteria by blocking the chaperone/usher pathway in Escherichia coli. It has also been shown that compounds derived from the peptidomimetic scaffold that the pilicides are based on can prevent both Aβ aggregation and curli formation. To facilitate optimizations towards the different targets, a new synthetic platform has been developed that enables fast and simple introduction of various substituents in position C-7 on the peptidomimetic scaffold. Importantly, this strategy also enables introduction of previously unattainable heteroatoms in this position. Pivotal to the synthetic strategy is the synthesis of a C-7 bromomethyl substituted derivative of the ring-fused dihydrothiazolo 2-pyridone pilicide scaffold. From this versatile and reactive intermediate various heteroatom-linked substituents could be introduced on the scaffold including amines, ethers, amides and sulfonamides. In addition, carbon-carbon bonds could be introduced to the sp(3)-hybridized bromomethyl substituted scaffold by Suzuki-Miyaura cross couplings. Evaluation of the 24 C-7 substituted compounds in whole-bacterial assays provided important structure-activity data and resulted in the identification of a number of new pilicides with activity as good or better than those developed previously.
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