A Purely Organic Tricarbanion

How many carbanions can an organic molecule accommodate? The formation of purely organic carbanions with multiple charges is challenging as charge stabilization cannot be achieved through metal coordination. Previously, only quaternary ammonium dicarbanion salts had been reported. By using highly electron‐deficient trifluoromethanesulfonyl (triflyl or Tf) groups, the formation of a purely organic tricarbanion has been realized for the first time.     

Can a Ketone Be More Reactive than an Aldehyde? Catalytic Asymmetric Synthesis of Substituted Tetrahydrofurans

O‐heterocycles bearing tetrasubstituted stereogenic centers are prepared via catalytic chemo‐ and enantioselective nucleophilic additions to ketoaldehydes, in which the ketone reacts preferentially over the aldehyde. Five‐ and six‐membered rings with both aromatic and aliphatic substituents, as well as an alkynyl substituent, are obtained. Moreover, 2,2,5‐trisubstituted and 2,2,5,5‐tetrasubstituted tetrahydrofurans are synthesized with excellent stereoselectivities. Additionally, the synthetic utility of the described method is demonstrated with a three‐step synthesis of the side chain of anhydroharringtonine.     

Selective,C-3 Friedel-Crafts acylation to generate functionally diverse,acetylated Imidazo[1,2-a]pyridine derivatives

Carbon-carbon bonds are integral for pharmaceutical discovery and development. Frequently, CC bond reactions utilize expensive catalyst/ligand combinations and/or are low yielding, which can increase time and expenditures in pharmaceutical development. To enhance CC bond formation protocols, we developed a highly efficient, selective, and combinatorially applicable Friedel-Crafts acylation to acetylate the C-3 position of imidazo[1,2-a]pyridines. The reaction, catalyzed by aluminum chloride, is both cost effective and more combinatorial friendly compared to acetylation reactions requiring multiple, stoichiometric equivalents of AlCl₃. The protocol has broad application in the construction of acetylated imidazo[1,2-a]pyridines with an extensive substrate scope. All starting materials are common and the reaction requires inexpensive, conventional heating methods for adaptation in any laboratory. Further, the synthesized compounds are predicted to possess GABA activity through a validated, GABA binding model. The developed method serves as a superior route to generate C-3 acetylated imidazo[1,2-a]pyridine building-blocks for combinatorial synthetic efforts.     

Crystal structure of (4α,4aα,8aα)-(±)-octahydro-2-(phenylmethyl)-2H-1,2-benzoxazin-4-ol, 4-methylbenzenesulfonate(ester)

The title compound, a bicyclic tetrahydro-1,2-oxazine, crystallizes in a monoclinic lattice, space group P2₁/c, with a = 12.9809(18)Å, b = 12.920(2)Å, c = 13.631(2)Å, = 110.713(12)°, and Z = 4. The structure found in the solid state for this conformationally mobile molecule shows the tosyl group in an axial position and a benzyl group in an equatorial position of the bicyclic system.     

On the Diophantine equation

If and are positive integers with and , then the equation of the title possesses at most one solution in positive integers and , with the possible exceptions of satisfying , and . The proof of this result relies on a variety of diophantine approximation techniques including those of rational approximation to hypergeometric functions, the theory of linear forms in logarithms and recent computational methods related to lattice-basis reduction. Additionally, we compare and contrast a number of these last mentioned techniques.

     

Langevin network model of myosin

Langevin mode theory and the coarse-grained elastic network model (ENM) for proteins are combined to yield the Langevin network model (LNM). Hydrodynamic radii of 6 A were assigned to each alpha-carbon on the basis of matching experimental translational and rotational diffusion constants of lysozyme, myoglobin, and hemoglobin with those calculated using a rigid body bead model with hydrodynamic interactions described by the Rotne-Prager tensor. LNM analysis of myosin II indicates that all ENM-like modes are overdamped at water viscosities. The low-frequency LNM modes in the pre-power stroke structure (PDB code: 1VOM) are substantially less mixed than the corresponding modes of the post-power stroke structure (1Q5G). Results from a four-bead model of the myosin "lever arm" indicate that coupling between modes increases as the array departs from linearity and are consistent with the results for 1VOM and 1Q5G. The decay times for all overdamped Langevin modes are shorter than the calculated rotational tumbling times found for lysozyme and myosin.     

Charge-transfer transitions in the vacuum-ultraviolet of protein circular dichroism spectra

Circular dichroism (CD) is widely used in the structural characterization and secondary structure determination of proteins. The vacuum UV region (below 190 nm), where charge-transfer transitions have an influence on the CD spectra, can be accessed using synchrotron radiation circular dichroism (SRCD) spectroscopy. Recently, charge-transfer transitions in a conformationally diverse set of dipeptides have been characterized ab initio using complete active space self-consistent field calculations, and the relevant charge distributions have been parametrized for use in the matrix method for calculations of protein CD. Here, we present calculations of the vacuum UV CD spectra of 71 proteins, for which experimental SRCD spectra and X-ray crystal structures are available. The theoretical spectra are calculated considering charge-transfer and side chain transitions. This significantly improves the agreement with experiment, raising the Spearman correlation coefficient between the calculated and the experimental intensity at 175 nm from 0.12 to 0.79. The influence of the conformation on charge-transfer transitions is analyzed in detail, showing that the n --> pi* charge-transfer transitions are most important in alpha-helical proteins, whereas in beta strand proteins the pi --> pi* charge-transfer transition along the chain in the amino- to carboxy-end direction is most dominant.     

Quantitative study of interactions between oxygen lone pair and aromatic rings: substituent effect and the importance of closeness of contact

Current models describe aromatic rings as polar groups based on the fact that benzene and hexafluorobenzene are known to have large and permanent quadrupole moments. This report describes a quantitative study of the interactions between oxygen lone pair and aromatic rings. We found that even electron-rich aromatic rings and oxygen lone pairs exhibit attractive interactions. Free energies of interactions are determined using the triptycene scaffold and the equilibrium constants were determined by low-temperature 1H NMR spectroscopy. An X-ray structure analysis for one of the model compounds confirms the close proximity between the oxygen and the center of the aromatic ring. Theoretical calculations at the MP2/aug-cc-pVTZ level corroborate the experimental results. The origin of attractive interactions was explored by using aromatic rings with a wide range of substituents. The interactions between an oxygen lone pair and an aromatic ring are attractive at van der Waals' distance even with electron-donating substituents. Electron-withdrawing groups increase the strength of the attractive interactions. The results from this study can be only partly rationalized by using the current models of aromatic system. Electrostatic-based models are consistent with the fact that stronger electron-withdrawing groups lead to stronger attractions, but fail to predict or rationalize the fact that weak attractions even exist between electron-rich arenes and oxygen lone pairs. The conclusion from this study is that aromatic rings cannot be treated as a simple quadrupolar functional group at van der Waals' distance. Dispersion forces and local dipole should also be considered.     

Steric,Electronic and Conformational Synergistic Effects in the Gold(I)-catalyzed α-C−H Bond Functionalization of Tertiary Amines**

Direct C−H bond functionalization is a useful strategy for the straightforward formation of C−C and C−Heteroatom bonds. In the present work, a unique approach for the challenging electrophilic Au-catalyzed α-C−H bond functionalization of tertiary amines is presented. Electronic, steric and conformational synergistic effects exerted by the use of a malonate unit in the substrate were key to the success of this transformation. This new reactivity was applied to the synthesis of tetrahydro-γ-carboline products which, under oxidative conditions, could be converted into valuable structural motifs found in bioactive alkaloid natural products.