Imaging Glycosylation In Vivo by Metabolic Labeling and Magnetic Resonance Imaging

Glycosylation is a ubiquitous post‐translational modification, present in over 50 % of the proteins in the human genome, 1 with important roles in cell–cell communication and migration. Interest in glycome profiling has increased with the realization that glycans can be used as biomarkers of many diseases, 2 including cancer. 3 We report here the first tomographic imaging of glycosylated tissues in live mice by using metabolic labeling and a gadolinium‐based bioorthogonal MRI probe. Significant N‐azidoacetylgalactosamine dependent T₁ contrast was observed in vivo two hours after probe administration. Tumor, kidney, and liver showed significant contrast, and several other tissues, including the pancreas, spleen, heart, and intestines, showed a very high contrast (>10‐fold). This approach has the potential to enable the rapid and non‐invasive magnetic resonance imaging of glycosylated tissues in vivo in preclinical models of disease.     

Disordering of phospholipid headgroups induced by a small amount of polyethylene oxide

We present a ³¹P NMR spectroscopy study of planar glass‐plate‐oriented multi‐bilayers of dimyristoylphosphatidylcholine (DMPC) with addition of polyethylene oxide (PEO). This work revealed the presence of a new component in the spectra that appeared only with addition of a small fraction of PEO (up to one PEO segment per dimyristoylphosphatidylcholine molecule) and disappeared when larger amounts of PEO were added. We explained this phenomenon as an effect of an inhomogeneous force field induced by the PEO molecules located at a certain depth in the lipid membrane interface region. Copyright © 2012 John Wiley & Sons, Ltd.     

Total synthesis of thiostrepton. Retrosynthetic analysis and construction of key building blocks

The first phase of the total synthesis of thiostrepton (1), a highly complex thiopeptide antibiotic, is described. After a brief introduction to the target molecule and its structural motifs, it is shown that retrosynthetic analysis of thiostrepton reveals compounds 23, 24, 26, 28, and 29 as potential key building blocks for the projected total synthesis. Concise and stereoselective constructions of all these intermediates are then described. The synthesis of the dehydropiperidine core 28 was based on a biosynthetically inspired aza-Diels-Alder dimerization of an appropriate azadiene system, an approach that was initially plagued with several problems which were, however, resolved satisfactorily by systematic investigations. The quinaldic acid fragment 24 and the thiazoline-thiazole segment 26 were synthesized by a series of reactions that included asymmetric and other stereoselective processes. The dehydroalanine tail precursor 23 and the alanine equivalent 29 were also prepared from the appropriate amino acids. Finally, a method was developed for the direct coupling of the labile dehydropiperidine key building block 28 to the more advanced and stable peptide intermediate 27 through capture with the highly reactive alanine equivalent 67 under conditions that avoided the initially encountered destructive ring contraction process.     

Antiviral nucleoside analogs

Chemistry of Heterocyclic Compounds - The minireview surveys the modification of native nucleosides as a result of which huge libraries of nucleoside analogs of various structures were synthesized....     

Selective Activation of Fluoroalkenes with N‐Heterocyclic Carbenes: Synthesis of N‐Heterocyclic Fluoroalkenes and Polyfluoroalkenyl Imidazolium Salts

Selective reactions between nucleophilic N,N′‐diaryl‐heterocyclic carbenes (NHCs) and electrophilic fluorinated alkenes afford NHC fluoroalkenes in high yields. These stable compounds undergo efficient and selective fluoride abstraction with Lewis acids to give polyfluoroalkenyl imidazolium salts. These salts react at Cβ with pyrrolidine to give ammonium fluoride‐substituted salts, which give rise to conjugated imidazolium‐enamine salts through loss of HF. Alternatively, reaction with 4‐(dimethylamino)‐pyridine provides a Cα‐pyridinium‐substituted NHC fluoroalkene. These compounds were studied using multinuclear NMR spectroscopy, mass spectrometry, and X‐ray crystallography. Insight into their electronic structure and reactivity was gained through the use of DFT calculations.     

Advances in the Study of Gas Hydrates by Dielectric Spectroscopy

The influence of kinetic hydrate inhibitors on the process of natural gas hydrate nucleation was studied using the method of dielectric spectroscopy. The processes of gas hydrate formation and decomposition were monitored using the temperature dependence of the real component of the dielectric constant ε′(T). Analysis of the relaxation times τ and activation energy ΔE of the dielectric relaxation process revealed the inhibitor was involved in hydrogen bonding and the disruption of the local structures of water molecules.