AK-2305GP_published_mainmanuscript - Issue in Honor of...

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Issue in Honor of Prof. Alain Krief ARKIVOC 2007 (x) 348-364 Stereoselectivity of the hydrogenation of galactofuranosyl exo glycals Audrey Caravano, a Weidong Pan, c and Stephane P. Vincent* a,c a Ecole Normale Superieure, Departement de Chimie, CNRS UMR 8642, 24 rue Lhomond, 75231 Paris Cedex 05, France c University of Namur, Laboratoire de Chimie-Bioorganique, Rue de Bruxelles 61 B-5000 Namur, Belgium Email: Stephane.vincent@fundp.ac.be Dedicated to Professor Alain Krief Abstract This work describes a study of the α / β -diastereoselectivity of the hydrogenation of phosphonylated exoglycals in the galactofuranose series. Nine exoglycals displaying sterically hindering groups on the α or the β face have been synthesized and hydrogenated using Pearlman's catalyst. These reactions gave the expected C -glycoside with good to excellent α - selectivities. Keywords: Exoglycal, C-glycoside, hydrogenation, phosphonate Introduction In the course of our study involving the exploration of the mechanism of glycosyl processing enzymes, we have developed an approach to generate C -glycosidic phosphonates in the galactofuranose series (Gal f ). First we developed conformational probes mimicking UDP-Gal f the substrate of key enzymes implied in the biosynthesis of the mycobacterial cell wall: UDP- galactose mutase (UGM) and Galacto furanosyl transferases. 1,2 We then prepared nucleotide- exoglycals, fluorinated 3 or not, 4 that displayed interesting time-dependent inactivation properties against UDP-galactose mutase. In our studies, exoglycals became key intermediates: for instance we found that once protected with four TBDMS groups, the enol ether could be hydrogenated selectively to give a α - phosphonate (Scheme 1) thus yielding a C -glycosidic analog of the natural Gal f -1- α -phosphate. 4 In some cases, glycoconjugates whose anomeric configuration is inverted compared to the natural substrate displayed interesting inhibition properties. 5 A survey of the literature in the Gal f series showed that there is no published method to synthesize the corresponding Gal f -1- β - ISSN 1424-6376 Page 348 © ARKAT-USA, Inc.
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Issue in Honor of Prof. Alain Krief ARKIVOC 2007 (x) 348-364 phosphonate. Therefore, we addressed the question of the obtention of β -phosphonates from phosphonylated exoglycals. The purpose of this study is to define the α / β stereoselectivity of the hydrogenation as a function of the protective group pattern of the phosphonylated exoglycal. Since both α and β diastereomers can be transformed into biologically relevant molecules, we found it interesting to assess the scope of these hydrogenations as a function of i) the selective steric hindrance of one of the two faces of the exoglycal ii) the directing effect of a OH group at the 2- or the 3- or the 5- position of the galactofuranosyl moiety (scheme 1). In the early eighties, it had already been acknowledged that hydroxyl-directed hydrogenations are of considerable generality. 6,7
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This note was uploaded on 02/17/2011 for the course CHEMISTRY 101 taught by Professor Csr during the Spring '11 term at University of Louisville.

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AK-2305GP_published_mainmanuscript - Issue in Honor of...

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