Synthetic utility and reactivity of N-alkynylazoles

textThe chemistry of N-alkynylazoles is a newly emerging area of chemistry with particular interest in heterocycle synthesis. Synthetic preparations of this class of molecule have shown an increasing presence in literature, however, the synthetic utility of this class of molecule remains underexplored. Herein, it is shown that N-alkynlazoles are a versatile synthetic intermediate and may have utility as covalent modifiers of cysteine residues in polypeptides.Pharmaceutical Science

Base-mediated generation of ketenimines from ynamides: direct access to azetidinimines by an imino staudinger synthesis

Ynamides were used as precursors for the in situ generation of highly reactive ketenimines which could be trapped with imines in a [2+2] cycloaddition. This imino Staudinger synthesis led to a variety of imino-analogs of β-lactams, namely azetidinimines (20 examples), that could be further functionalized through a broad range of transformations

Synthesis of 2-iodoynamides and regioselective [2+2] cycloadditions with ketene

The first synthesis of 2-iodoynamides is described as well as the first [2+2] cycloadditions of ketene with iodo alkynes.National Institutes of Health (U.S.) (GM 28273)Boehringer Ingelheim PharmaceuticalsMerck Research Laboratorie

Progress towards the synthesis of tetracyclic heteroaromatic compounds via tandem benzannulation-cyclization strategies

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2012.Cataloged from PDF version of thesis.Includes bibliographical references.A tandem benzannulation-cyclization strategy was successfully applied to the synthesis of a tetracyclic heteroaromatic compound expected to have interesting electronic properties. Benzannulation of a diazo ketone and a ynamide yielded a highly substituted aniline that was cyclized to indole according to protocols developed in our laboratory previously.by Galina Mamaliga.S.B

Palladium(II)-Catalysed Aminocarbonylation of Terminal Alkynes for the Synthesis of 2-Ynamides: Addressing the Challenges of Solvents and Gas Mixtures

2‐Ynamides can be synthesised through Pd(II) catalysed oxidative carbonylation, utilising low catalyst loadings. A variety of alkynes and amines can be used to afford 2‐ynamides in high yields, whilst overcoming the drawbacks associated with previous oxidative methods, which rely on dangerous solvents and gas mixtures. The use of [NBu(4)]I allows the utilisation of the industrially recommended solvent ethyl acetate. O(2) can be used as the terminal oxidant, and the catalyst can operate under safer conditions with low O(2) concentrations

Staphylococcus aureus sortase a-mediated incorporation of peptides: Effect of peptide modification on incorporation

The endogenous Staphylococcus aureus sortase A (SrtA) transpeptidase covalently anchors cell wall-anchored (CWA) proteins equipped with a specific recognition motif (LPXTG) into the peptidoglycan layer of the staphylococcal cell wall. Previous in situ experiments have shown that SrtA is also able to incorporate exogenous, fluorescently labelled, synthetic substrates equipped with the LPXTG motif (K(FITC)LPETG-amide) into the bacterial cell wall, albeit at high concentrations of 500 μM to 1 mM. In the present study, we have evaluated the effect of substrate modification on the incorporation efficiency. This revealed that (i) by elongation of LPETG-amide with a sequence of positively charged amino acids, derived from the C-terminal domain of physiological SrtA substrates, the incorporation efficiency was increased by 20-fold at 10 μM, 100 μM and 250 μM; (ii) Substituting aspartic acid (E) for methionine increased the incorporation of the resulting K(FITC)LPMTG-amide approximately three times at all concentrations tested; (iii) conjugation of the lipid II binding antibiotic vancomycin to K(FITC)LPMTG-amide resulted in the same incorporation levels as K(FITC)LPETG-amide, but much more efficient at an impressive 500-fold lower substrate concentration. These newly developed synthetic substrates can potentially find broad applications in for example the in situ imaging of bacteria; the incorporation of antibody recruiting moieties; the targeted delivery and covalent incorporation of antimicrobial compounds into the bacterial cell wall

Diamine ligands in copper-catalyzed reactions

The utility of copper-mediated cross-coupling reactions has been significantly increased by the development of mild reaction conditions and the ability to employ catalytic amounts of copper. The use of diamine-based ligands has been important in these advances and in this perspective we discuss these systems, including the choice of reaction conditions and applications in the synthesis of pharmaceuticals, natural products and designed materials.National Institutes of Health (U.S.) (Grant GM-58160

The intermolecular hydro-oxycarbonylation of internal alkynes: current state of the art

The authors acknowledge the Spanish MINECO (projects CTQ2013-40591-P and CTQ2016-75986-P) and the Gobierno del Principado de Asturias (project GRUPIN14-006) for financial support. J. F. thanks MINECO and ESF for the award of a Juan de la Cierva contract