Diarylmethane synthesis through Re_2O_7-catalyzed bimolecular dehydrative Friedel–Crafts reactions

This manuscript describes the application of Re_2O_7 to the syntheses of diarylmethanes from benzylic alcohols through solvolysis followed by Friedel–Crafts alkylation. The reactions are characterized by broad substrate scope, low catalyst loadings, high chemical yields, and minimal waste generation. The intermediate perrhenate esters are superior leaving groups to chlorides and bromides in these reactions. The polarity and water sequestering capacity of hexafluoroisopropyl alcohol are critical to the success of these processes. Re_2O_7 is a precatalyst for HOReO_3, which serves as a less costly and easily handled promoter for these reactions. Oxorhenium catalysts selectively activate alcohols in the presence of similarly substituted acetates, indicating a unique chemoselectivity and mechanism in comparison to Brønsted acid catalysis

Diarylmethane synthesis through Re_2O_7-catalyzed bimolecular dehydrative Friedel–Crafts reactions

This manuscript describes the application of Re_2O_7 to the syntheses of diarylmethanes from benzylic alcohols through solvolysis followed by Friedel–Crafts alkylation. The reactions are characterized by broad substrate scope, low catalyst loadings, high chemical yields, and minimal waste generation. The intermediate perrhenate esters are superior leaving groups to chlorides and bromides in these reactions. The polarity and water sequestering capacity of hexafluoroisopropyl alcohol are critical to the success of these processes. Re_2O_7 is a precatalyst for HOReO_3, which serves as a less costly and easily handled promoter for these reactions. Oxorhenium catalysts selectively activate alcohols in the presence of similarly substituted acetates, indicating a unique chemoselectivity and mechanism in comparison to Brønsted acid catalysis

Recognition of the Minor Groove of DNA by Hairpin Polyamides Containing α-Substituted-β-Amino Acids

Incorporation of the flexible amino acid β-alanine (β) into hairpin polyamides composed of N-methylpyrrole (Py) and N-methylimidazole (Im) amino acids is required for binding to DNA sequences longer than seven base pairs with high affinity and sequence selectivity. Pairing the α-substituted-β-amino acids (S)-isoserine (^SIs), (R)-isoserine (^RIs), β-aminoalanine (Aa), and α-fluoro-β-alanine (Fb) side-by-side with β in hairpin polyamides alters DNA binding affinity and selectivity relative to the parent polyamide containing a β/β pairing. Quantitative DNase I footprinting titration studies on a restriction fragment containing the sequences 5‘-TGCNGTA-3‘ (N = A, T, G, and C) show that the polyamide ImPy^SIsImPy-γ-PyPyβImPy-β-Dp (^SIs/β pairing) binds to N = T (K_a = 4.5 × 10^9 M^(-1)) in preference to N = A (K_a = 6.2 × 10^8 M^(-1)). This result stands in contrast to the essentially degenerate binding of the parent ImPyβImPy-γ-PyPyβImPy-β-Dp (β/β pairing) to N = T and N = A, and to the slight preference of ImPyβImPy-γ-PyPy^SIsImPy-β-Dp (β/^SIs pairing) to N = A over N = T. Additionally, this study reveals that incorporation of ^RIs, Aa, and Fb into polyamides significantly reduces binding affinity. Therefore, DNA binding in the minor groove is sensitive to the stereochemistry, steric bulk, and electronics of the substituent at the α-position of β-amino acids in hairpin polyamides containing β/β pairs

Selective targeting of microglia by quantum dots

<p>Abstract</p> <p>Background</p> <p>Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases.</p> <p>Methods</p> <p>Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies.</p> <p>Results</p> <p>In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity.</p> <p>Conclusions</p> <p>These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.</p

Synthesis of Bridged Inside–Outside Bicyclic Ethers through Oxidative Transannular Cyclization Reactions

The classical geometry of the 6-<i>endo</i> transition state for nucleophilic additions into oxocarbenium ions can be perturbed by incorporating the reactive groups into medium-sized rings, leading to the formation of 2,6-<i>trans</i>-dialkyl tetrahydropyrans. The bicyclic products exhibit inside–outside stereoisomerism, as seen in numerous macrolide natural products

Synthesis of Sulfur-Containing Heterocycles through Oxidative Carbon–Hydrogen Bond Functionalization

Vinyl sulfides react rapidly and efficiently with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to form α,β-unsaturated thiocarbenium ions through oxidative carbon–hydrogen bond cleavage. These electrophiles couple with appended π-nucleophiles to yield sulfur-containing heterocycles through carbon–carbon bond formation. Several nucleophiles are compatible with the procedure, and the reactions generally proceed through readily predictable transition states

Synthesis of Bridged Inside–Outside Bicyclic Ethers through Oxidative Transannular Cyclization Reactions

The classical geometry of the 6-<i>endo</i> transition state for nucleophilic additions into oxocarbenium ions can be perturbed by incorporating the reactive groups into medium-sized rings, leading to the formation of 2,6-<i>trans</i>-dialkyl tetrahydropyrans. The bicyclic products exhibit inside–outside stereoisomerism, as seen in numerous macrolide natural products