Accommodation of alpha-substituted residues in the beta-peptide 12-helix: expanding the range of substitution patterns available to a foldamer scaffold

Beta-amino acid oligomers composed exclusively of homochiral trans-2-aminocyclopentanecarboxylic acid (ACPC) residues and/or related pyrrolidine-based residues are known to favor a specific helical secondary structure that is defined by 12-membered ring C=O(i)- -H-N(i+3) hydrogen bonds ("12-helix"). The 12-helix is structurally similar to the familiar alpha-helix and therefore represents a source of potential alpha-helix-mimics. The 12-helix will be most useful in this regard if this conformational scaffold can be employed to arrange specific sets of protein-like side chains in space. Here we examine whether the 12-helix tolerates insertion of acyclic beta-amino acid residues bearing a substituent in the alpha-position ("beta(2)-residues"). Seventeen homologous beta-peptide heptamers have been prepared in which one to four beta(2)-residues reside among ACPC and/or pyrrolidine residues. Circular dichroism comparisons suggest that beta(2)-residues have a lower 12-helical propensity than do residues preorganized by a five-membered ring, as expected, but that beta-peptides containing beta(2)-residues at one or two of the seven positions retain a significant preference for 12-helix formation. These results indicate that a limited number of beta(2)-residues can be used to introduce side chains at specific positions along the surface of a 12-helix.     

Functionalized foldamers: synthesis and characterization of a glycosylated beta-peptide 314-helix conveying the TN-antigen

Herein we describe the design, synthesis, and solution structure of a novel type of conjugate composed of a naturally occurring bio-active ligand bound to an artificial peptidomimetic backbone; in this first report on such functionalized foldamers we utilized a beta-peptide as backbone and a GalNAc carbohydrate residue as ligand.     

Origins of the high 14-helix propensity of cyclohexyl-rigidified residues in beta-peptides

[structure: see text] beta-Peptides containing residues derived from trans-2-aminocyclohexanecarboxylic acid (ACHC) display high population of 14-helical secondary structure in aqueous solution. We show that hydrophobic interactions between cyclohexyl rings are not responsible for this conformation-promoting effect, and that polar groups may be attached to the cyclohexyl ring without diminishing the effect.     

Cyclopropanation of protected chiral,acyclic allylic alcohols: expedient access to the anti-cyclopropylcarbinol derivatives

The diastereoselective cyclopropanation of silyl-protected chiral allylic alcohols using Shi's carbenoid (TFA-Et(2)Zn-CH(2)I(2)) gave access to the anti-cyclopropylcarbinyl silyl ethers with excellent diastereocontrol. The level of stereocontrol was shown to depend on the sizes of the protective group and the allylic substituent. [reaction: see text]     

A pyrone remodeling strategy to access diverse heterocycles: application to the synthesis of fascaplysin natural products

The synthesis of diverse N-fused heterocycles, including the pyrido[1,2-a]indole scaffold, using an efficient pyrone remodeling strategy is described. The pyrido[1,2-a]indole core was demonstrated to be a versatile scaffold that can be site-selectively functionalized. The utility of this novel annulation strategy was showcased in a concise formal synthesis of three fascaplysin congeners.

The synthesis of diverse N-fused heterocycles, including the pyrido[1,2-a]indole scaffold, using an efficient pyrone remodeling strategy is described.     

Molecular imprinting: a dynamic technique for diverse applications in analytical chemistry

Continuous advances in analyzing complex matrices, improving reliability and simplicity, and performing multiple simultaneous assays with extreme sensitivity are increasing. Several techniques have been developed for the quantitative assays of analytes at low concentrations (e.g., high-pressure liquid chromatography, gas chromatography, immunoassay and the polymerase chain reaction technique). To achieve highly specific and sensitive analysis, high affinity, stable, and specific recognition agents are needed. Although biological recognition agents are very specific and sensitive they are labile and/or have a low density of binding sites. During the past decade molecular imprinting has emerged as an attractive and highly accepted tool for the development of artificial recognition agents. Molecular imprinting is achieved by the interaction, either noncovalent or covalent, between complementary groups in a template molecule and functional monomer units through polymerization or polycondensation. These molecularly imprinted polymers have been widely employed for diverse applications (e.g., in chromatographic separation, drug screening, chemosensors, catalysis, immunoassays etc.) owing to their specificity towards the target molecules and high stability against physicochemical perturbations. In this review the advantages, applications, and recent developments in molecular imprinting technology are highlighted.     

A unified access to diverse heteroaromatic scaffolds using the radical chemistry of xanthates

The degenerate transfer of xanthates allows generally difficult radical transformations, such as intermolecular additions to unactivated alkenes and cyclisations onto aromatic and heteroaromatic rings, to be accomplished under very practical experimental conditions. This translates into numerous approaches for the construction or modification of heteroaromatic structures. The present report aims to provide a brief overview of the various synthetic possibilities, with particular emphasis on medicinally interesting families of compounds.     

Correlation of the side-chain hubs with the functional residues in DNA binding protein structures

The structure networks of DNA-binding proteins have been constructed and analyzed. The detailed analysis of the networks indicates a strong relation between the positions of the residues interacting with DNA and those that form extensive interactions within the protein structure (called hubs). This study shows that the functional residues in these proteins are held in place by efficient scaffolding of the structure using side-chain interactions, thus highlighting the role of these side-chain hubs with respect to the functional residues in the protein structure.     

Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products

Cultured soil microorganisms have provided a rich source of natural-product chemistry. Because only a tiny fraction of soil microbes from soil are readily cultured, soil might be the greatest untapped resource for novel chemistry. The concept of cloning the metagenome to access the collective genomes and the biosynthetic machinery of soil microflora is explored here.     

Stereoselective dichlorination of allylic alcohol derivatives to access key stereochemical arrays of the chlorosulfolipids

Dichlorination of (Z)-allylic trichloroacetates efficiently and stereoselectively generates the syn,syn hydroxydichloride stereotriad that is prevalent in the understudied polychlorinated sulfolipid class of natural products. Further, the dichlorination of a (Z)-allylic chlorohydrin affords with high selectivity a stereotetrad present in one of the chlorosulfolipids.     

Enantioselective total synthesis of erogorgiaene: applications of asymmetric Cu-catalyzed conjugate additions of alkylzincs to acyclic enones

The first enantioselective synthesis of erogorgiaene (1), an inhibitor of mycobacterium tuberculosis, is disclosed. The total synthesis highlights the utility of asymmetric conjugate additions (ACA) of alkylzincs to acyclic alpha,beta-unsaturated ketones catalyzed by peptidic phosphine ligands and (CuOTf)(2).C(6)H(6). Moreover, several critical attributes of this catalytic C-C bond-forming reaction are illustrated in the context of the total synthesis; these include the significance of various structural features of the amino acid-based chiral ligands and the chiral ligand's effectiveness in reactions involving achiral and chiral substrates. In addition, the total synthesis showcases some of the special properties of nonphosphine Ru complex 3 as a highly effective catalyst for olefin cross-metathesis.     

Hartwig-Buchwald amination on solid supports: a novel access to a diverse set of 1H-benzotriazoles

Hartwig-Buchwald amination reactions of bromo- and chloroarenes were performed on solid supports with triazene-linked arenes. Immobilized 2-haloarenes were treated with diverse primary amines and anilines at 100 degrees C under palladium catalysis to yield N-substituted 2-aminoarenes. The latter were alternatively formed through reaction of bromo- and chloroarenes with immobilized primary 2-aminobenzenes. Subsequent acidic cleavage furnished 1H-benzotriazoles in high purities. The two described routes allow a broad range of the substitution pattern of N-substituted 1H-benzotriazoles.     

Current progress of molybdenum carbide-based materials for electrocatalysis: potential electrocatalysts with diverse applications

Electrocatalysts are the cores of many electrochemical reactions including hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), nitrogen reduction reaction (NRR), and CO₂ reduction reaction (CO₂RR). Recent advances in research have demonstrated the potentials of molybdenum carbide-based catalysts for these reactions arising out of their unique electronic structure and physicochemical properties. In this review, we systematically summarize the recent advances of molybdenum carbide-based catalysts in these electrochemical processes. The corresponding synthesis strategies, structure and electrocatalytic performance of the catalysts are discussed and the relationships of the process-structure-property are highlighted. In addition, the catalytic mechanisms are analyzed based on the structure characterization and theoretical calculations results. Finally, the existing challenges and future perspectives are put forward for further development of molybdenum carbide-based catalysts.     

A tactically novel alternative to acyclic stereoselection based on the concept of a replicating chiron — access to 1,3-polyols

(S)-Glutamic acid is used as a chiral template to construct seven carbon subunits containing alternating hydroxyl groups with stereochemical control. Enantiomeric and/or diastereomeric 3,5-dideoxy-heptitols are thus obtained.     

Exploring the unique reactivities of heterobicyclic tetrazoles—access to functionally diverse and versatile heterocyclic scaffolds

The benzylic hydrogen atom in oxabicyclic tetrazoles such as (6R,8R)-(8-phenyl-5,6-dihydro-8H-tetrazolo[5,1-c][1,4]oxazin-6-yl)-alkanols (A, X=CH₂OH) is highly acidic, being alkylated in preference to a hydroxymethyl group with NaH and active alkyl halides. The enantioenriched products B now contain a phenyl and alkyl group on a stereogenic benzylic carbon atom. The products are subject to β-elimination to give 1-{1-[3-propenyl]-1H-tetrazol-5-yl}-1-phenyl-alkanols. Cleavage of the propenyl chain leads to chiral non-racemic 1-phenyl-1-(1H-tetrazol-5-yl)-alkanols C. Free-radical ‘anomeric’ azidation of the oxabicyclic tetrazoles followed by reduction and ring closure with inversion of configuration produces azabicyclic tetrazoles D as constrained functionalized piperazines.     

Cyclic and acyclic sulfonimides in reactions with Rh(II)-ketocarbenoids: a new access to chemoselective O-functionalization of the imidic carbonyl groups

Catalytic decomposition of diazoacetylacetone, diazoacetoacetic, diazomalonic, and diazoacetic esters using dirhodium tetraacetate in the presence of isothiazol-3(2H)-one 1,1-dioxides and a number of N-(arenesulfonyl)carboxamides in solutions of methylene chloride or dichloroethane gives rise to O-alkylation of the imidic carbonyl groups by Rh(II)-carbenoids and the formation of O-alkylimidates as the final products. The reaction proceeds with high chemoselectivity via carbonyl ylides and offers a powerful method for the synthesis in good yields of the imidates with polyfunctional O-alkyl groups. On the basis of X-ray analysis and 1H- and 13C-NMR studies it was shown that the resulting acyclic O-alkylimidates have the E-configuration in the solid state and in solution. Unlike acyclic analogues, the cyclic carbonyl ylide derived from substituted diazosaccharin by intramolecular cyclization of the appropriate diketocarbenoid is capable of reacting with DMAD in a 1,3-cycloaddition process.     

Development of tip-enhanced optical spectroscopy for biological applications: a review

Tip-enhanced optical spectroscopy is an approach that holds a good deal of promise for the nanoscale characterisation of matter. Tip-enhanced Raman spectroscopy (TERS) has been demonstrated on a variety of samples: inorganic, organic and biological. Imaging using TERS has been shown for carbon nanotubes due to their high scattering efficiency. There are a number of compelling motivations to consider alternative approaches for biological samples; most importantly, the potential for heat damage of biomolecules and long acquisition times. These issues may be addressed through the development of tip-enhanced coherent anti-Stokes Raman scattering microscopy.