From Glucose to Cyclooctanic Carbaglucose: A New Class of Carbohydrate Mimetics

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COMMUNICATIONS 2466 WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000 1433-7851/00/3914-2466 $ 17.50+.50/0 Angew. Chem. Int. Ed. 2000, 39, No. 14 From Glucose to Cyclooctanic Carbaglucose: A New Class of Carbohydrate Mimetics Wei Wang, Yongmin Zhang, Matthieu Sollogoub, and Pierre Sinay È* Synthetic oligosaccharides have recently emerged as po- tential therapeutic agents. [1] A possible in vivo hydrolysis of such drugs by various glycosidases has stimulated the search for nonhydrolyzable oligosaccharide mimetics. One option is to replace the endocyclic oxygen atom of aldohexopyranosyl residues by a methylene group. The resulting 5a-carbasugars are hydrolytically stable analogues, and the chemical synthesis of the 5a-carbaaldohexopyranoside family has been largely developed. [2] An intriguing alternative is to use a cyclooctane ring as a framework for the OH groups of the carbohydrate. For instance, the replacement of the endocyclic oxygen atom in methyl b-d-glucopyranoside (1) by one methylene group would result in a cyclohexanic mimetic 2, whereas the replacement by three methylene groups would give a novel type of cyclooctanic carbohydrate mimetic 3 (Scheme 1). The rationale behind this proposal is that the conformation and conformational equilibration of cyclooctane derivatives [3] may offer interesting new distributions of hydroxy groups Scheme 1. Methyl b-d-glucopyranoside (1) as well as the cyclohexanic (2) and cyclooctanic (3) analogues. compared to those available through the classical pseudorota- tional itinerary [4] of pyranoid rings. The incorporation of these so far undescribed carbocyclic sugar mimetics in oligosac- charide chains is thus of interest in terms of the resulting biological responses, such as glycosidase inhibition, a feature which may benefit from the easy access to nonclassical conformers. The thermal or triisobutylaluminum (TIBAL) promoted Claisen rearrangement of 2-methylene-6-vinyl-tetrahydropyr- an, which affords cyclooctanic derivatives by insertion of a C 2 unit, has been elegantly developed by Paquette et al. [5] for the synthesis of natural products with eight-membered rings. It has recently been applied in the carbohydrate field, either in the form of a thermal reaction, [6] or in the form of a smooth Al III -catalyzed process [7] (Scheme 2). Scheme 2. Thermal or TIBAL-catalyzed Claisen rearrangement of unsa- turated monosaccharide derivatives. Bn PhCH 2 ; Bz PhCO. As shown in Scheme 3, the cyclooctanol derivative 6, the enantiomer of the previously prepared cyclooctanol 5, was smoothly obtained in 96 % yield from the TIBAL-catalyzed sigmatropic rearrangement of the gluco derivative 12, which in turn was easily derived from methyl a-d-glucopyranoside in an eight-step sequence. Methylation of 6 gave 13 which, upon regio- and stereo- selective hydroboration, was converted in 60 % yield into the cyclooctanol derivative 14 (Scheme 4). Oxidation of 14 gave the cyclooctanone 15, and subsequent treatment with the Tebbe reagent [Cp 2 Ti(m-Cl)(m-CH 2 )AlMe 2 ] generated the methylene derivative 16. Regioselective hydroboration of 16 gave the cyclooctanic mimetic 17 and the a-l-ido isomer 18, which were separated by flash chromatography on silica gel (Scheme 5). The boat ± chair conformation for compound 17 (Scheme 6) is assigned on the basis of the 3 J couplings in the 1 H NMR spectrum. The H1 ± H5 NOE confirms the b-d-gluco config- uration. The interpretation of the NMR spectrum of the a-l- diffractometer with a smart CCD detector (Mo Ka radiation, l 0.71073 , w scans, 3.6 2q 60.748). All in all 10 263 reflections were detected (6663 independent reflections) and 5869 were classified as observed. The structure was solved by direct methods and refined against F 2 . Hydrogen atoms were placed at calculated positions and refined dependent on the adjacent non-hydrogen atoms (riding model). The refinement of the 331 varied parameters converged to R 0.0425 for 6663 reflections with I > 2s(I) and wR2 0.0900 for all reflections. Min./max. transmission 3.790/2.057 e 3 . The structure was solved with SIR-97 [16] and refined with SHELXL-97. [17] Crystallo- graphic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-141108. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: ( 44) 1223-336-033 ; e-mail : [email protected]). [14] In poorly solvating solvents the reaction of TlTpms tBu with ZnBr 2 leads to not only the expected C 3v -symmetrical species but also to a C s - symmetrical compound that has yet to be identified. [15] D. L. Reger, J. E. Collins, D. L. Jameson, R. K. Castellano, Inorg. Synth. 1998, 32, 63 ± 65. [16] A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C. Giaco- vazzo, A, Guagliardi, A. G. G. Moliterni, G. Polidori, R. Spagna, J. Appl. Crystallogr. 1999, 32, 115 ± 119. [17] G. M. Sheldrick, SHELXL 97 , Programs for Crystal Structure Analysis (Release 97 ± 2), University of Göttingen, Germany, 1997 . [*] Prof. P. Sinay È, Dr. W. Wang, Dr. Y. Zhang, Dr. M. Sollogoub Ecole Normale Supe  rieure De Âpartement de Chimie, UMR 8642, 24 rue Lhomond, 75231 Paris, Cedex 05 (France) Fax: ( 33) 1-44323397 E-mail: [email protected] Supporting information for this article is available on the WWW under http://www.wiley-vch.de/home/angewandte/ or from the author.

Transcript of From Glucose to Cyclooctanic Carbaglucose: A New Class of Carbohydrate Mimetics

Page 1: From Glucose to Cyclooctanic Carbaglucose: A New Class of Carbohydrate Mimetics

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