The synthesis of a discovery library of 80 3,4-dehydroproline amides was achieved in a four-step reaction sequence from easily accessible 3-aminoallene-3-carboxylate methyl esters. Diversification of these proline mimics was introduced at five different sites: the substituents at the 3-pyrroline unit (R1, R2, R3), at the nitrogen (R4), and the C-terminus (R5). The 3-pyrroline scaffold was synthesized in excellent yields by a silver-catalyzed intramolecular cyclization of aminoallenes, followed by N-functionalization reactions. Maximum diversity was introduced in the final step of the reaction sequence by taking advantage of the carboxylic acid handle of the 3-pyrroline subunit. Amide coupling reactions using polystyrene-carbodiimide (PS-carbodiimide) and 1-hydroxybenzotriazole (HOBt) under microwave irradiation led to 3,4-dehydroproline amides that were obtained in purities greater than 85% by LC/MS/ESLD after scavenging the excess HOBt on a silica-bound carbonate SPE cartridge.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/cc070011p | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clinical studies of blood-borne Extracellular vesicles in psychiatry: A systematic review.
J Psychiatr Res
January 2025
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379, Oslo, Norway; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway; Department for Mechanical, Electronics and Chemical Engineering, Oslo Metropolitan University, Oslo, Norway.
Biomarkers for the diagnosis and clinical management of psychiatric disorders are currently lacking. Extracellular vesicles (EVs), lipid membrane-encapsulated vesicles released by cells, hold promise as a source of biomarkers due to their ability to carry molecules that reflect the status of their donor cells and their ubiquitous presence in biofluids. This review examines the literature on EVs in biofluids from psychiatric disorder patients, and discuss how the published studies contribute to our understanding of the pathophysiology of these conditions and to the discovery of potential biomarkers.
View Article and Find Full Text PDFPro-cumulin addition in a biphasic in vitro oocyte maturation system modulates human oocyte and cumulus cell transcriptomes.
Mol Hum Reprod
January 2025
Follicle Biology Laboratory, Research Group Genetics, Reproduction and Development, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Biphasic in vitro oocyte maturation (IVM) can be offered as a patient-friendly alternative to conventional ovarian stimulation in in vitro fertilization (IVF) patients predicted to be hyper-responsive to ovarian stimulation. However, cumulative live birth rates after IVM per cycle are lower than after conventional ovarian stimulation for IVF. In different animal species, supplementation of IVM media with oocyte-secreted factors (OSFs) improves oocyte developmental competence through the expression of pro-ovulatory genes in cumulus cells.
View Article and Find Full Text PDFA multiscale molecular structural neural network for molecular property prediction.
Mol Divers
January 2025
Key Laboratory for Macromolecular Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, 710119, People's Republic of China.
Molecular Property Prediction (MPP) is a fundamental task in important research fields such as chemistry, materials, biology, and medicine, where traditional computational chemistry methods based on quantum mechanics often consume substantial time and computing power. In recent years, machine learning has been increasingly used in computational chemistry, in which graph neural networks have shown good performance in molecular property prediction tasks, but they have some limitations in terms of generalizability, interpretability, and certainty. In order to address the above challenges, a Multiscale Molecular Structural Neural Network (MMSNet) is proposed in this paper, which obtains rich multiscale molecular representations through the information fusion between bonded and non-bonded "message passing" structures at the atomic scale and spatial feature information "encoder-decoder" structures at the molecular scale; a multi-level attention mechanism is introduced on the basis of theoretical analysis of molecular mechanics in order to enhance the model's interpretability; the prediction results of MMSNet are used as label values and clustered in the molecular library by the K-NN (K-Nearest Neighbors) algorithm to reverse match the spatial structure of the molecules, and the certainty of the model is quantified by comparing virtual screening results across different K-values.
View Article and Find Full Text PDFIsolation and Bioactivity of Natural Products from sp. MA37.
Molecules
January 2025
Marine Biodiscovery Centre, Department of Chemistry, School of Natural and Computing Sciences, University of Aberdeen, Old Aberdeen AB24 3UE, UK.
The isolation and characterization of bioactive metabolites from species continue to represent a vital area of research, given their potential in natural product drug discovery. In this study, we characterize a new siderophore called legonoxamine I, together with a known compound, streptimidone, from the talented soil bacterium sp. MA37, using chromatographic techniques and spectroscopic analysis.
View Article and Find Full Text PDFConstruction of a Library of Fatty Acid Esters of Hydroxy Fatty Acids.
Molecules
January 2025
Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) have emerged as extraordinary bioactive lipids, exhibiting diverse bioactivities, from the enhancement of insulin secretion and the optimization of blood glucose absorption to anti-inflammatory effects. The intricate nature of FAHFAs' structure reflects a synthetic challenge that requires the strategic introduction of ester bonds along the hydroxy fatty acid chain. Our research seeks to create an effective methodology for generating varied FAHFA derivatives.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!