Search results for "combinatorial"
showing 10 items of 1208 documents
Chemical and enzymatic synthesis of glycopeptides
1995
Progress recently made in the synthesis of biologically relevant N- and O-glycopeptides is illustrated by examples. In this context, developments in the preparation of complex saccharide side chains and in the subsequent coupling to peptide portions is described. Special emphasis is given to the synthesis of Lewis antigen-type structures. Furthermore, modern methods in solid phase peptide syntheses utilizing glycosylated building blocks are presented. Recent advances in glycopeptide syntheses employing enzymatic methods in deprotection steps as well as in peptide/saccharide chain elongation are reported.
Protein Flexibility and Preorganization in the Design of Enzymes. The Kemp Elimination Catalyzed by HG3.17
2015
A recently designed enzyme, HG3.17, obtained by directed evolution, has shown a catalytic activity close to natural enzymes. Hybrid QM/MM molecular dynamics simulations for the Kemp elimination in this new enzyme have provided a deep insight into the origin of its catalytic efficiency. In this case, we have first demonstrated the presence of different conformations with significantly different reactivity. The larger reactivity is related with a better electrostatic preorganization of the environment that creates a more favorable electrostatic potential for the reaction to proceed. In HG3.17, efforts to improve the catalytic properties must be focused in possible mutations increasing the pre…
Chemoenzymatic-Chemical Synthesis of a (2-3)-Sialyl T Threonine Building Block and Its Application to the Synthesis of the N-Terminal Sequence of Leu…
2001
Protection of all functional groups of the carbohydrate portion of the chemoenzymatically synthesized sialyl T threonine ester 1 (R=R1 =H, R2 =tBu, Fmoc=9-fluorenylmethoxycarbonyl) and subsequent acidolysis of the tert-butyl ester afforded the building block 2 (R=Ac, R1 =Me, R2 =H). The latter is a useful tool in the solid-phase synthesis of the N-terminal sequence 3 of the leukemia-associated leukosialin.
Electrochemical synthesis of sulfamides.
2021
Herein we demonstrate the first electrochemical synthesis protocol of symmetrical sulfamides directly from anilines and SO2 mediated by iodide. Sulfamides are an emerging functional group in drug design. Highlights are the direct use of SO2 from a stock solution and no necessity of any supporting electrolyte. Overall, the reaction has been demonstrated for 15 examples with yields up to 93%.
ChemInform Abstract: Solution-, Solid-Phase, and Fluorous Synthesis of β,β-Difluorinated Cyclic Quaternary α-Amino Acid Derivatives: A Comparative St…
2008
The diastereoselective synthesis of cyclic β,β-difluorinated α-amino acid derivatives bearing a quaternary stereocenter is described. The process relies on the chemo- and diastereoselective addition of allylic organometallic reagents to fluorinated α-imino esters and a subsequent ring-closing metathesis reaction (RCM). Complete selectivity in the nucleophilic addition was achieved with (R)-phenylglycinol methyl ether as a chiral auxiliary. The resulting amino acids were introduced into peptide chains, which could facilitate the preparation of potentially bioactive dipeptide derivatives. In addition, the solution synthesis of these cyclic fluorinated α-amino acids was successfully adapted to…
Recurrence of the oxazole motif in tubulin colchicine site inhibitors with anti-tumor activity
2021
Abstract Because of its wide spectrum of targets and biological activities, the oxazole ring is a valuable heterocyclic scaffold in the design of new therapeutic agents with anticancer, antiviral, antibacterial, anti-inflammatory, neuroprotective, antidiabetic and antidepressant properties. The presence of two heteroatoms, oxygen and nitrogen, offers possible interactions (hydrogen, hydrophobic, van der Waals or dipoles bonds) with a broad range of receptors and enzymes. Furthermore, the oxazole core conjugates low cytotoxicity with improved compound solubility and is well suited to structural modifications such as substitution with different groups and condensation to aromatic, heteroaroma…
Direct Visualization of Pyrrole Reactivity upon Confinement within a Cyclodextrin Metal–Organic Framework
2019
Metal–organic frameworks can be used as porous templates to exert control over polymerization reactions. Shown here are the possibilities offered by these crystalline, porous nanoreactors to capture highly-reactive intermediates for a better understanding of the mechanism of polymerization reactions. By using a cyclodextrin framework the polymerization of pyrrole is restricted, capturing the formation of terpyrrole cationic intermediates. Single-crystal X-ray diffraction is used to provide definite information on the supramolecular interactions that induce the formation and stabilization of a conductive array of cationic complexes.
Pauson–Khand reaction of fluorinated compounds
2020
The Pauson–Khand reaction (PKR) is one of the key methods for the construction of cyclopentenone derivatives, which can in turn undergo diverse chemical transformations to yield more complex biologically active molecules. Despite the increasing availability of fluorinated building blocks and methodologies to incorporate fluorine in compounds with biological interest, there have been few significant advances focused on the fluoro-Pauson–Khand reaction, both in the inter- and intramolecular versions. Furthermore, the use of vinyl fluorides as olefinic counterparts had been completely overlooked. In this review, we collect the advances both on the stoichiometric and catalytic intermolecular an…
Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers
2012
In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low temperatures, 56 structurally diverse multidentate ligands were screened in a model system that uses copper iodide in acetonitrile with potassium phosphate as the base. The ligands differed largely in their performance, but no privileged structural class could be identified.
Detoxication Strategy of Epoxide Hydrolase—The Basis for a Novel Threshold for Definable Genotoxic Carcinogens
2004
From our recent work on the three-dimensional structure of epoxide hydrolases we theoretically deduced the likelihood of a two-step catalytic mechanism that we and others have subsequently experimentally confirmed. Analysis of the rate of the two steps by us and by others show that the first step—responsible for removal of the reactive epoxide from the system—works extraordinarily fast (typically three orders of magnitude faster than the second step), sucking up the epoxide like a sponge. Regeneration of the free enzyme (the second step of the catalytic mechanism) is slow. This becomes a toxicological problem only at doses of the epoxide that titrate the enzyme out. Our genotoxicity work s…