A synthetic route to the tripeptide unit of geodiamolide-B

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Yttrium-Catalyzed Amine–Silane Dehydrocoupling: Extended Reaction Scope with a Phosphorus-Based Ligand

The scope of the catalytic dehydrocoupling of primary and secondary amines with phenylsilanes has been investigated using [Y­{N­(SiMe₃)₂}₃] and a four-coordinate analogue bearing a cyclometalated phosphonium methylide ligand. Inclusion of the phosphorus-based ligand on yttrium results in increased substrate scope in comparison to the tris­(amide) analogue. While reversible C–H bond activation of the cyclometalated ligand was observed in stoichiometric experiments, D-labeling experiments and DFT calculations suggest that reversible ligand activation is not involved in silazane formation under catalytic conditions. We suggest that the extended reaction scope with the four-coordinate yttrium phosphonium methylide complex relative to the three-coordinate yttrium (tris)­amide complex is a result of differences in the ease of amine inhibition of catalysis

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Sultones and Sultines via a Julia-Kocienski Reaction of Epoxides

We thank the EPSRC/Syngenta for a CASE Ph.D. Studentship (to G.M.T.S. under grant EP/J50029X/1), the EPSRC UK National Mass Spectrometry Facility at Swansea University and the EPSRC UK National Crystallography Service Facility at Southampton University.37 We are indebted to Andrew Plant and Janice Black (Syngenta) for the initial suggestion of using the combination of LiN(SiMe3)2/CH2Cl2 and Matthew Reid (Syngenta) for NMR assistance

Transition metal catalyzed element–element′ additions to alkynes

The efficient and stereoselective synthesis of, or precursors to, multi-substituted alkenes has attracted substantial interest due to their existence in various industrially and biologically important compounds. One of the most atom economical routes to such alkenes is the transition metal catalyzed hetero element–element′ π-insertion into alkynes. This article provides a thorough up-to-date review on this area of chemistry, including discussions on the mechanism, range of Esingle bondE′ bonds accessible and the stoichiometric/catalytic transition metal mediators employed