Sequentially photocleavable protecting groups in solid-phase synthesis

[reaction: see text] A sequential solid-phase peptide synthesis was developed using both photolabile linker and protecting groups. The chromatic sequential lability between a tert-butyl ketone-derived linker (sensitive to irradiation at 305 nm) and a nitroveratryloxycarbonyl (NVOC) group (sensitive at 360 nm) was exploited to prepare Leu-Enkephalin in a 55% overall yield. This new strategy allows the preparation of peptides in essentially neutral medium, by avoiding the use of common deprotection reagents such as trifluoroacetic acid or piperidine.     

Electron Impact Induced Fragmentation of Aromatic Alkoxyimines II [5]. Formation and Transformation of Heterocyclic Radical Cations in the Gas Phasea

 The molecular ion 1 of N-(n-propoxy)benzaldimine I rearranges by an 1,5-H-shift to the δ-distonic ion 2 which subsequently cyclizes to the α-distonic ion 3. Homolytic cleavage of the N–O bond in 3 results in the δ-distonic ion 4 which expels CH₂O leading to the β-distonic ion 5. Ion 5 is also formed from the molecular ions of tetrahydrooxazines II and III and from M^+• of phenylazetidine IVa. In a subsequent step, ion 5 cyclizes to the N-protonated 3,4-dihydroisoquinolinium ion 6. The syntheses of II–IV and their derivatives are described.     

Synthesis, structure, and dynamics of six-membered metallacoronands and metallodendrimers of iron and indium

In the reaction of the N-substituted diethanolamines (H(2)L(1-3)) (1-3) with calcium hydride followed by addition of iron(III) or indium(III) chloride, the iron wheels [Fe(6)Cl(6)(L(1))(6)] (4) and [Fe(6)Cl(6)(L(2))(6)] (6) or indium wheels [In(6)Cl(6)(L(1))(6)] (5), [In(6)Cl(6)(L(2))(6)] (8) and [In(6)Cl(6)(L(3))(6)] (9) were formed in excellent yields. Exchange of the chloride ions of 6 by thiocyanate ions afforded [Fe(6)(SCN)(6)(L(2))(6)] (7). Whereas the structures of 4, 5 and 7 were determined unequivocally by single-crystal X-ray analyses, complexes 8 and 9 were characterised by NMR spectroscopy. Contrary to what is normally presumed, the scaffolds of six-membered metallic wheels are not generally rigid, but rather undergo nondissociative topomerisation processes. This was shown by variable temperature (VT) (1)H NMR spectroscopy for the indium wheel [In(6)Cl(6)(L(1))(6)] (5) and is highlighted for the enantiotopomerisation of one indium centre [ 1/6[S(6)-5]<==>[1/6[S(6)-5']]. The self-assembly of metallic wheels, starting from diethanolamine dendrons, is an efficient strategy for the convergent synthesis of metallodendrimers.     

NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors

Binding events of ligands to receptors are the key for an understanding of biological processes. Gaining insight into protein-protein and protein-ligand interactions in solution has recently become possible on an atomic level by new NMR spectroscopic techniques. These experiments identify binding events either by looking at the resonance signals of the ligand or the protein. Ideally, both techniques together deliver a complete picture of ligand binding to a receptor. The approaches discussed in this review allow screening of compound libraries as well as a detailed identification of the groups involved in the binding events. Also, characterization of the binding strength and kinetics is possible, competitive binding as well as allosteric effects can be identified, and it has even been possible to identify ligand binding to intact viruses and membrane-bound proteins.     

MPW1K Performs Much Better than B3LYP in DFT Calculations on Reactions that Proceed by Proton-Coupled Electron Transfer (PCET)

DFT calculations have been performed with the B3LYP and MPW1K functional on the hydrogen atom abstraction reactions of ethenoxyl with ethenol and of phenoxyl with both phenol and alpha-naphthol. Comparison with the results of G3 calculations shows that B3LYP seriously underestimates the barrier heights for the reaction of ethenoxyl with ethenol by both proton-coupled electron transfer (PCET) and hydrogen atom transfer (HAT) mechanisms. The MPW1K functional also underestimates the barrier heights, but by much less than B3LYP. Similarly, comparison with the results of experiments on the reaction of phenoxyl radical with alpha-naphthol indicates that the barrier height for the preferred PCET mechanism is calculated more accurately by MPW1K than by B3LYP. These findings indicate that the MPW1K functional is much better suited than B3LYP for calculations on hydrogen abstraction reactions by both HAT and PCET mechanisms.     

The RuO4-catalysed dihydroxylation, ketohydroxylation and mono oxidation--novel oxidation reactions for the synthesis of diols and alpha-hydroxy ketones

Alpha-hydroxy ketones are versatile intermediates for the synthesis of complex molecular architectures and subunits of a variety of natural products. Different approaches towards the synthesis of this important functional group combination have been elaborated. The present article summarises our research on the field of RuO4-catalysed oxidations of alkenes that resulted in the development of the first RuO4-catalysed ketohydroxylation of olefins. Mechanistic investigations of both dihydroxylation and ketohydroxylation led to the discovery of the first regioselective catalytic mono oxidation of vic-diols, which was applied in a two-step sequence of asymmetric dihydroxylation and regioselective mono oxidation to furnish enantiopure alpha-hydroxy ketones with both predictable regioselectivity and absolute configuration.     

Electron impact induced fragmentation of aromatic N-alkoxy-imines I. Ring closure in (M-CH2O)+• ions by intramolecular aromatic substitution

Summary N-Butoxy- and N-propoxy-imines derived fromo-,m-, andp-substituted benzaldehydes (X = F, Cl, Br, I) decompose upon electron impact to the respective aldoximes by loss of C _n H_2n and competitivelyvia 1,5-distonic radical cations by loss of CH₂O to 1,3-distonic ions which eliminate H and/or a halogen atom in the course of homolytic aromatic substitution, giving rise to cyclic (M-CH₂O-H)⁺ or (M-CH₂O-X )⁺ ions.Dedicated with warm regards to Prof. Dr.D. Seebach, Zürich, on the occasion of his 60^th birthday     

Ultrafast proton-coupled electron-transfer dynamics in pyrene-modified pyrimidine nucleosides: model studies towards an understanding of reductive electron transport in DNA.

5-(Pyren-1-yl)-2'-deoxyuridine (PydU) and 5-(Pyren-1-yl)-2'-deoxycytidine (PydC) were used as model nucleosides for DNA-mediated reductive electron transport (ET) in steady-state fluorescence and femtosecond time-resolved transient absorption spectroscopy studies. Excitation of the pyrene moiety in PydU and PydC leads to an intramolecular electron transfer that yields the pyrenyl radical cation and the corresponding pyrimidine radical anion (dU.- and dC.-. By comparing the excited state dynamics of PydC and PydU, we derived information about the energy difference between the two pyrimidine radical anion states. To determine the influence of protonation on the rates of photoinduced intramolecular ET, the spectroscopic investigations were performed in acetonitrile, MeCN, and in water at different pH values. The results show a significant difference in the basicity of the generated pyrimidine radical anions and imply an involvement of proton transfer during electron hopping in DNA. Our studies revealed that the radical anion dC.- is being protonated even in basic aqueous solution on a picosecond time scale (or faster). These results suggest that protonation of dC.- may also occur in DNA. In contrast, efficient ET in PydU could only be observed at low pH values (< 5). In conclusion, we propose--based on the free energy differences and the different basicities--that only dT.- but not dC.- can participate as an intermediate charge carrier for excess electron migration in DNA.     

Alkenes as ketol surrogates-a new approach toward enantiopure acyloins

[reaction: see text] Enantiopure alpha-hydroxy ketones are important building blocks in organic synthesis. This paper describes the use of cyclic ruthenates for the first catalytic regioselective oxidation of vic-diols to alpha-ketols. The combination of RuCl3/Oxone/NaHCO3 was used in a two-step sequence of asymmetric dihydroxylation and regioselective monooxidation for the synthesis of a broad scope of enantiopure acyloins.