An efficient synthetic pathway to the possible stereoisomers of skeletally diverse heterocyclic small molecules is presented. The change in shape brought about by different intramolecular cyclizations of diastereoisomeric amino propargylic alcohols is quantified using principal moment-of-inertia (PMI) shape analysis.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883853 | PMC |
http://dx.doi.org/10.1021/ol100914b | DOI Listing |
Molecules
January 2025
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.
Numerous emerging chemotherapeutic agents incorporate -heterocyclic fragments in their structures, with the quinoline skeleton being particularly significant. Our recent works have focused on glycoconjugates of 8-hydroxyquinoline (8-HQ), which demonstrated enhanced bioavailability and solubility compared to their parent compounds, although they fell short in selectivity. In this study, our objective was to improve the selectivity of glycoconjugates by replacing the oxygen atom with nitrogen by substituting the 8-HQ moiety with 8-aminoquinoline (8-AQ).
View Article and Find Full Text PDFJ Am Soc Mass Spectrom
December 2024
Center for Genomic Science Innovation, University of Wisconsin Madison, Madison, Wisconsin 53706, United States.
Protein footprinting is a useful method for studying protein higher order structure and conformational changes induced by interactions with various ligands via addition of covalent modifications onto the protein. Compared to other methods that provide single amino acid-level structural resolution, such as cryo-EM, X-ray diffraction, and NMR, mass spectrometry (MS)-based methods can be advantageous as they require lower protein amounts and purity. As with other MS-based proteomic methods, such as post-translational modification analysis, enrichment techniques have proven necessary for both optimal sensitivity and sequence coverage when analyzing highly complex proteomes.
View Article and Find Full Text PDFJ Org Chem
November 2024
Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 2030, 128 43 Praha 2, Czech Republic.
Azlactone is an important starting material for synthesizing amino acids containing a quaternary α-carbon. In this study, we have developed a sequential "one-pot" procedure involving an enantioselective spirocyclization reaction followed by acidic azlactone opening, which led to amino acid derivatives. The key step of this procedure is a spirocyclization between propargylated azlactones and enals by using a cooperative catalytic approach that combines chiral secondary amine and achiral Pd(0) complexes.
View Article and Find Full Text PDFJ Med Chem
October 2024
Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
Cystobactamids have a unique oligoarylamide structure and exhibit broad-spectrum activity against Gram-negative and Gram-positive bacteria. In this study, the central α-amino acid of the cystobactamid scaffold was modified to address the relevance of stereochemistry, hydrogen bonding and polarity by 33 derivatives. As demonstrated by three matched molecular pairs, l-amino acids were preferred over d-amino acids.
View Article and Find Full Text PDFOrg Lett
September 2024
Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune-411008, India.
We present a methodology yielding 3,4-dihydro-2-1,4-oxazine by cyclization of -propargyl -sulfonyl amino alcohols using silver triflate as a catalyst at ambient temperature. Additionally, we showcase the applicability of this methodology in solid phase peptide synthesis (SPPS) to introduce the oxazine heterocyclic ring into short peptides containing serine and threonine. Notably, Rink amide resin supported the on-resin formation of 3,4-dihydro-2-1,4-oxazine, while 2-CTC resin facilitated the oxazine formation in a one-pot process involving peptide cleavage, deprotection, and subsequent C-O ring formation, thus offering a versatile method for the late-stage modification of peptides.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!