AK-2305GP_published_mainmanuscript

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

Info iconThis preview shows pages 1–3. Sign up to view the full content.

View Full Document Right Arrow Icon
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.
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
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
Background image of page 2
Image of page 3
This is the end of the preview. Sign up to access the rest of the document.

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.

Page1 / 17

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

This preview shows document pages 1 - 3. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online