92 research outputs found
Reactivity of TEMPO anion as a nucleophile and its applications for selective transformations of haloalkanes or acyl halides to aldehydes
Sodium 2,2,6,6-tetramethylpiperidine-N-oxide (TEMPO−Na+), generated by reduction of TEMPO· with sodium naphthalenide in THF, reacted with alkyl halides or acyl halides to produce O-alkylated or acylated TEMPOs, which were in turn oxidized with mCPBA or reduced with DIBAL-H to afford the corresponding aldehydes, thus accomplishing a new protocol for the halides-carbonyls conversion.</p
Prospects in computational molecular medicine: a millennial mega-project on peptide folding
During the second half of the 20th century, Molecular Computations have
reached to a level that can revolutionize chemistry. The next target
will be structural biology, which will be followed soon by Molecular
Medicine. The present paper outlines where we are at, in this field, at
the end of the 20th century, and in what direction the development may
take in the new millennium. In view of the gigantic nature of the
problem, it is suggested that a suitably designed cooperative
Millennial Mega-project might accelerate our schedule. (C) 2000
Elsevier Science B.V. All rights reserved
Nickel-Catalyzed Alkyl-Alkyl Cross-Couplings of Fluorinated Secondary Electrophiles: A General Approach to the Synthesis of Compounds having a Perfluoroalkyl Substituent
Exploiting the Imidazolium Effect in Base-free Ammonium Enolate Generation:Synthetic and Mechanistic Studies
The authors thank the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC Grant Agreement no. 279850 (CMY, THW, JET). ADS thanks the Royal Society for a Wolfson Merit Award.N-Acyl imidazoles and catalytic isothiourea hydrochloride salts function as ammonium enolate precursors in the absence of base. Enantioselective Michael addition-cyclization reactions using different α,β-unsaturated Michael acceptors have been performed to form dihydropyranones and dihydropyridinones with high stereoselectivity. Detailed mechanistic studies using RPKA have revealed the importance of the “imidazolium” effect in ammonium enolate formation and have highlighted key differences with traditional base-mediated processes.PostprintPeer reviewe
Synthesis of fused indoline-cyclobutanone derivatives via an intramolecular [2+2] cycloaddition
We thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1, R.M.N.) for funding. We thank the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013) ERC grant agreement no. 279850 (A.D.S.). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. We also thank the EPSRC UK National Mass Spectrometry Service at Swansea. The research data supporting this publication can be accessed at https://doi.org/10.17630/00aff760-0732-438f-a9d1-30c7cf3a87a0A serendipitously-discovered process for the synthesis of heterocyclic products containing a novel fused indoline-cyclobutanone ring system is reported. This process is believed to take place through in situ generation of a ketene intermediate, followed by intramolecular [2+2] cycloaddition with a pendant enamide. The formation of a ketene intermediate in this process is significant as the reaction conditions employed are analogous to those commonly used in tertiary amine Lewis base catalysis, where the potential intermediacy of ketenes is an important consideration that is often overlooked.PostprintPeer reviewe
Antioxidant properties of MitoTEMPOL and its hydroxylamine
Piperidine nitroxides such as TEMPOL have been widely used as antioxidants in vitro and in vivo. MitoTEMPOL is a mitochondria-targeted derivative of TEMPOL designed to protect mitochondria from the oxidative damage that they accumulate, but once there is rapidly reduced to its hydroxylamine, MitoTEMPOL-H. As little is known about the antioxidant efficacy of hydroxylamines, this study has assessed the antioxidant activity of both MitoTEMPOL and MitoTEMPOL-H. The hydroxylamine was more effective at preventing lipid-peroxidation than MitoTEMPOL and decreased oxidative damage to mitochondrial DNA caused by menadione. In contrast to MitoTEMPOL, MitoTEMPOL-H has no superoxide dismutase activity and its antioxidant actions are likely to be mediated by hydrogen atom donation. Therefore, even though MitoTEMPOL is rapidly reduced to MitoTEMPOL-H in cells, it remains an effective antioxidant. Furthermore, as TEMPOL is also reduced to a hydroxylamine in vivo, many of its antioxidant effects may also be mediated by its hydroxylamine
Social Class
Discussion of class structure in fifth-century Athens, historical constitution of theater audiences, and the changes in the comic representation of class antagonism from Aristophanes to Menander
Generating a Generation of Proteasome Inhibitors: From Microbial Fermentation to Total Synthesis of Salinosporamide A (Marizomib) and Other Salinosporamides
The salinosporamides are potent proteasome inhibitors among which the parent marine-derived natural product salinosporamide A (marizomib; NPI-0052; 1) is currently in clinical trials for the treatment of various cancers. Methods to generate this class of compounds include fermentation and natural products chemistry, precursor-directed biosynthesis, mutasynthesis, semi-synthesis, and total synthesis. The end products range from biochemical tools for probing mechanism of action to clinical trials materials; in turn, the considerable efforts to produce the target molecules have expanded the technologies used to generate them. Here, the full complement of methods is reviewed, reflecting remarkable contributions from scientists of various disciplines over a period of 7 years since the first publication of the structure of 1
Experimental evidence for competitive N O and O C bond homolysis in gas-phase alkoxyamines
- …