Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Aβ-peptide aggregation inhibitors

Åberg, Veronica; Norman, Fredrik; Chorell, Erik; Westermark, Andreas; Olofsson, Anders; Sauer‐Eriksson, A. Elisabeth; Almqvist, Fredrik

doi:10.1039/b503294f

Cited by 57 publications

(38 citation statements)

References 30 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, we reasoned that acrylic acid may be a suitable cycloaddition partner for both reasons: (1) it is an excellent dienophile toward 5-alkoxyoxazoles in HDA reactions (neither thermal nor catalytic 3e activation is required); (2) the carboxylic acid group thus generated on the pyridine core would benefit from the presence of an ortho-hydroxy substituent, 15 known to facilitate the protodecarboxylation reaction. Consequently, the methyl multijuguinate 4 would be accessible using the hetero-Diels− Alder reaction as key step, between conveniently substituted 19 It should be stressed that in our case, addition of a mild base such as K 2 CO 3 did not increase the yield as observed by Gooβen, but resulted in partial decomposition of the reaction mixture probably due to the presence of a base-sensitive ester group. 20 Consequently, the methyl multijuguinate 4 was obtained in four steps in 29% overall yield from commercially available ethyl lactate (Scheme 3).…”

Section: Scheme 2 Possible Reaction Mechanism To Form 2fmentioning

confidence: 52%

Expeditious Microwave-Assisted Synthesis of 5-Alkoxyoxazoles from α-Triflyloxy Esters and Nitriles

2012

View full text Add to dashboard Cite

A rapid and general access to diversely substituted 5-alkoxyoxazoles 2 (i.e., R(1), R(2) = alkyl, phenyl) from easily accessible α-triflyloxy/hydroxy esters 1 and nitriles with good yields (41-76%) is reported. The versatility of the cyclization is shown for a range of substrates with high selectivity toward triflates over mesylates and proved to be compatible with sensitive functional groups. As an illustration of this transformation, the first synthesis of the recently isolated hydroxypyridine methyl multijuguinate 4 was achieved in four steps through a hetero Diels-Alder reaction of the 5-alkoxyoxazole and acrylic acid, followed by a protodecarboxylation reaction.

show abstract

Section: Scheme 2 Possible Reaction Mechanism To Form 2fmentioning

confidence: 52%

Expeditious Microwave-Assisted Synthesis of 5-Alkoxyoxazoles from α-Triflyloxy Esters and Nitriles

2012

View full text Add to dashboard Cite

show abstract

“…A screen of compounds originally designed to inhibit the elaboration of E. coli P pili yielded a set of small molecules capable of inhibiting amyloid formation of Aβ [99, 100]. These compounds have since been subject to extensive chemical modification and assayed for biological activity against several amyloid substrates including curli [28, 91, 101].…”

Section: Folding Intermediates Can Be Probed Using Antibodies and mentioning

confidence: 99%

Curli biogenesis: Order out of disorder

Evans

Chapman

2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

205

224

View full text Add to dashboard Cite

Many bacteria assemble extracellular amyloid fibers on their cell surface. Secretion of proteins across membranes and the assembly of complex macromolecular structures must be highly coordinated to avoid the accumulation of potentially toxic intracellular protein aggregates. Extracellular amyloid fiber assembly poses an even greater threat to cellular health due to the highly aggregative nature of amyloids and the inherent toxicity of amyloid assembly intermediates. Therefore, temporal and spatial control of amyloid protein secretion is paramount. The biogenesis and assembly of the extracellular bacterial amyloid curli is an ideal system for studying how bacteria cope with the many challenges of controlled and ordered amyloid assembly. Here, we review the recent progress in the curli field that has made curli biogenesis one of the best-understood functional amyloid assembly pathways.

show abstract

“…The 2-pyridone compounds have a rigid bicyclic structure, which maintains the compounds in a straight conformation that mimics a β-strand (118). Altered 2-pyridone compounds were constructed that had increased solubility and were used to inhibit the type 1 pilus assembly in UTI89 via interruption of the chaperone-usher interaction (122, 123). …”

Section: Chemical and Protein Modulation Of Csga Amyloid Formationmentioning

confidence: 99%

The Biology of the Escherichia coli Extracellular Matrix

2015

View full text Add to dashboard Cite

Chapter Summary Escherichia coli (E. coli) is one of the world’s best-characterized organisms, as it has been extensively studied for over a century. However, most of this work has focused on E. coli grown under laboratory conditions that do not faithfully simulate its natural environments. Therefore, the historical perspectives on E. coli physiology and life cycle are somewhat skewed toward experimental systems that feature E. coli growing logarithmically in a test tube. Typically a commensal bacterium, E. coli resides in the lower intestines of a slew of animals. Outside of the lower intestine, E. coli can adapt and survive in a very different set of environmental conditions. Biofilm formation allows E. coli to survive, and even thrive, in environments that do not support the growth of planktonic populations. E. coli can form biofilms virtually everywhere; in the bladder during a urinary tract infection, on in-dwelling medical devices, and outside of the host on plants and in the soil. The E. coli extracellular matrix, primarily composed of the protein polymer named curli and the polysaccharide cellulose, promotes adherence to organic and inorganic surfaces, and resistance to desiccation, the host immune system and other antimicrobials. The pathways that govern E. coli biofilm formation, cellulose production, and curli biogenesis will be discussed in this book chapter, which concludes with insights into the future of E. coli biofilm research and potential therapies.

show abstract

Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Aβ-peptide aggregation inhibitors

Cited by 57 publications

References 30 publications

Expeditious Microwave-Assisted Synthesis of 5-Alkoxyoxazoles from α-Triflyloxy Esters and Nitriles

Expeditious Microwave-Assisted Synthesis of 5-Alkoxyoxazoles from α-Triflyloxy Esters and Nitriles

Curli biogenesis: Order out of disorder

The Biology of the Escherichia coli Extracellular Matrix

Contact Info

Product

Resources

About