10 research outputs found

    A versatile synthetic approach toward diversity libraries using monosaccharide scaffolds

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    The pyranose scaffold is unique in its ability to position pharmacophore substituents in various ways in 3D space, and unique pharmacophore scanning libraries could be envisaged that focus on scanning topography rather than diversity in the type Of substituents. Approaches have been described that make use of amine and acid functionalities on the pyranose scaffolds to append substituents, and this has enabled the generation of libraries of significant structural diversity. Our general aim was to generate libraries of pyranose-based drug-like mimetics, where the substituents are held close to the scaffold, in order to obtain molecules with better defined positions for the pharmacophore substituents. Here we describe the development of a versatile synthetic route toward peptide mimetics build oil 2-amino pyranose scaffolds. The method allows introduction of a wide range of substituent types, it is regio- and stereospecific, and the later diversity steps are performed on solid phase. Further, the same process was applied oil glucose mid allose scaffolds, in the exemplified cases, and is likely adaptable to other pyranose building blocks. The methods developed in this work give access to molecules that position the three selected binding elements in various 3D orientations oil a pyranose scaffold and have been applied for the production of a systematically diverse library of several hundred monosaccharide-based mimetics

    Oligocene mammals from Ethiopia and faunal exchange between Afro-Arabia and Eurasia

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    Afro-Arabian mammalian communities underwent a marked transition near the Oligocene/Miocene boundary at approximately 24 million years (Myr) ago. Although it is well documented that the endemic paenungulate taxa were replaced by migrants from the Northern Hemisphere, the timing and evolutionary dynamics of this transition have long been a mystery because faunas from about 32 to 24 Myr ago are largely unknown(1). Here we report a late Oligocene fossil assemblage from Ethiopia, which constrains the migration to postdate 27 Myr ago, and yields new insight into the indigenous faunal dynamics that preceded this event. The fauna is composed of large paenungulate herbivores and reveals not only which earlier taxa persisted into the late Oligocene epoch but also demonstrates that one group, the Proboscidea, underwent a marked diversification. When Eurasian immigrants entered Afro-Arabia, a pattern of winners and losers among the endemics emerged: less diverse taxa such as arsinoitheres became extinct, moderately species-rich groups such as hyracoids continued into the Miocene with reduced diversity, whereas the proboscideans successfully carried their adaptive radiation out of Afro-Arabia and across the world.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62496/1/nature02102.pd
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