This paper concerns peptidomimetic scaffolds that can present side-chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analog local pairs of amino acids (including non-contiguous ones) in any secondary structure, ie they are universal peptidomimetics. To illustrate this concept we designed a set of four peptidomimetic scaffolds (1 -4). Libraries based on these were made bearing side-chains corresponding to many of the proteinderived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together peptidomimetics based on scaffolds 1 -4 can adopt conformations that resemble almost any combination of local amino acid side-chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) is outlined.

This project was undertaken to demonstrate the potential of asymmetric hydrogenations mediated by the chiral, carbene-oxazoline analogue of Crabtree's catalyst "cat" in asymmetric hydrogenations of allylic amine derivatives of amino acids. Peripheral features of the substrates (protecting groups, functional groups related by redox processes, and alkene geometries) were varied to optimize the stereochemical vectors exerted by the substrate and align them with the catalyst vector. N-Acetyl-protected, O-TBDPS-protected allylic substrates 9a-e emerged as the best for this reaction; syn-products were formed from the E-alkenes, while the Z-isomers gave anti-target materials, both with high diastereoselectivities. This study featured asymmetric catalysis to elaborate optically active substrates into more stereochemically complex chirons; we suggest that the approach used, optimization of stereocontrol by varying peripheral aspects of the substrate, tends to be easier than de novo catalyst design for each substrate type. In other words, optimization of the substrate vector is likely to be more facile than enhancement of the catalyst vector via ligand modifications.

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Asymmetric Syntheses of α-Methyl γ-Amino Acid Derivatives. -In the presence of IRC, allyl amines of type (I) and (IV) smoothly undergo asymmetric hydrogenation to afford title compounds like (II) and (III). The nature of the substituents and the configuration of the C=C double bond influence the stereochemical outcome. -(ZHU, Y.; KHUMSUBDEE, S.; SCHAEFER, A.; BURGESS*, K.; J. Org. Chem. 76 (2011) 18, 7449-7457, http://dx.doi.org/10.1021/jo201215c ; Dep. Chem., Tex. A&M Univ., College Station, TX 77842, USA; Eng.) -Jannicke 04-172