Cross-strand histidine-aromatic interactions enhance acyl-transfer rates in beta-hairpin peptide catalysts.

A reactive tagging methodology was used to select the species most reactive to an acylation reagent from a solid phase library of beta hairpin peptides. Hits bearing an electron-rich aromatic residue across strand from a reactive histidine were found to competitively become N-acylated. In addition to displaying rapid N-acylation rates the hit peptide was additionally deacylated in the presence of a nucleophile, thus closing a putative catalytic cycle. Variants of the hit peptide were studied to elucidate both the magnitude (up to 18,000-fold over background, kcat/kuncat = 94,000,000, or 45-fold over Boc-histidine methyl ester) and mechanism of acyl transfer catalysis. A combination of CH-π, cation-π and HisH(+)-O interactions in the cationic imidazole transition state is implicated in the rate acceleration, in addition to the fidelity of the beta hairpin fold. Moreover, NMR structural data on key intermediates or models thereof suggest that a key feature of this catalyst is the ability to access several different stabilizing conformations along the catalysis reaction coordinate.

Structure and reactivity of mixed alkali metal alkoxide/aryloxide catalysts.

The average solution aggregation state of the ester interchange catalyst 1, obtained by mixing 1 equiv of NaOt-Bu and 3 equiv of NaOC(6)H(4)-4-t-Bu, was determined to be 4.0 by vapor pressure osmometry (VPO) in THF. Low-temperature (1)H NMR spectra of 1 indicated that the THF solution contained a mixture of tetrameric clusters. On the basis of symmetry arguments and the sensitivity of the different species to the alkoxide/aryloxide ratio, the compounds were determined to be mixed clusters with 0:4, 1:3, 2:2, and 3:1 mixtures of the NaOt-Bu and NaOC(6)H(4)-4-t-Bu components. On a per -Ot-Bu basis, each cluster has a similar absolute activity, though the aryloxide-rich catalysts are significantly longer-lived. Unlike 1, catalysts containing ortho-substituted aryloxides, 2, do not give a strictly statistical distribution of clusters, and the activities of these catalysts depend on steric and electronic factors, though the absolute rate differences are not large.

Asymmetric Pt(II)-catalyzed ene reactions: counterion-dependent additive and diphosphine electronic effects.

[reaction: see text]. Catalysis of the glyoxylate-ene reaction by dicationic P2Pt(II) complexes is subject to anion-dependent additive effects. For [((S)-MeOBiphep)Pt](OTf)2 catalysts, acidic phenols such as 3-CF3-C6H3OH or C6F5OH provide substantial rate increases but do not affect the more active SbF6-based catalysts. Enantioselectivity and reactivity also increased with diphosphine basicity, with 4-t-Bu-substituted MeOBiphep ligands yielding the highest enantioselectivities.