Synthesis of Di-Branched Heptasaccharide by One-Pot Glycosylation Using Seven Independent Building Blocks Hiroshi Tanaka, Masaatsu Adachi, Hirokazu Tsukamoto, ² Takeji Ikeda, Haruo Yamada, ‡ and Takashi Takahashi* Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan ttakashi@o.cc.titech.ac.jp Received July 31, 2002 ABSTRACT We describe an efficient synthesis of di-branched heptasaccharide 1 having phytoalexin elicitor activity in soybeans by one-pot glycosylation. The synthesis involves chemo- and regioselective sequential six-step glycosylations using seven independent building blocks and sequential removal of acyl- and benzyl ether-type protecting groups. The coupling of seven building blocks requires only four chemoselective activitable leaving groups of glycosyl donors. Both the glycosylation and deprotection reactions can be achieved utilizing a parallel manual synthesizer. Recent recognition of the important biological roles of oligosaccharides 1 has driven the development of new meth- odologies for the synthesis of such compounds on solid phase and in solution. 2,9e These methodologies have already allowed the synthesis of a combinatorial library 3-9,10j,l,13 of tri- and tetrasaccharides. However library synthesis of more complex oligosaccharides such as penta- or hexasaccharides is still difficult. Therefore efficient methodology for the such oligosaccharides would be required. * To whom correspondence should be addressed. Tel: +81-3-5734-2120. Fax +81-3-5734-2884. ² Current address: Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai 980-8578, Japan. ‡ Current address: Department of Chemistry, Faculty of Science Okayama University of Science, Okayama, Ridai 1-1, Okayama 700-0005, Japan. (1) (a) Varki, A.; Cunnings, R.; Esko, J.; Freeze, H.; Hart, G.; Marth, J. Essentials of Glycobiology; Cold Spring Harbor Laboratory Press: New York, 1999. (b) Ernst, B.; Hart, G. W.; Sinay, P. Carbohydrates in Chemistry and Biology; Wiley-VCH: Weinheim, 2000; Vols. 3 and 4. (2) (a) Ernst, B.; Hart, G. W.; Sinay, P. Carbohydrates in Chemistry and Biology; Wiley-VCH: Weinheim, 2000; Vols. 1 and 2. For recent reviews of oligosaccharide synthesis, see: (b) Davis, B. G. J. Chem. Soc., Perkin Trans. 1 2000, 2137-2160. (c) Nicolaou, K. C.; Mitchell, H. J. Angew. Chem., Int. Ed. 2001, 40, 1576-1624. (d) Sears, P.; Wong, C.-H. Science 2001, 291, 2344-2350. (3) Liang, R.; Yan, L.; Loebach, J.; Ge, M.; Uozumi, Y.; Sekanina, K.; Horan, N.; Gildersleeve, J.; Thompson, C.; Smith, A.; Biswas, K.; Still, W. C.; Kahne, D. Science 1996, 274, 1520-1522. (4) (a) Kanie, O.; Barresi, F.; Ding, Y.; Labbe, J.; Otter, A.; Forsberg, L. S.; Ernst, B.; Hindsgaul, O. Angew. Chem., Int. Ed. Engl. 1995, 34, 2720- 2722. (b) Ding, Y.; Labbe, J.; Kanie, O.; Hindsgaul, O. Bioorg. Med. Chem. 1996, 4, 683-692. (5) (a) Boons, G.-J.; Heskamp, B.; Hout, F. Angew. Chem., Int. Ed. Engl. 1996, 35, 2845-2847. (b) Zhu, T.; Boons, G.-J. Angew. Chem., Int. Ed. 1998, 37, 1898-1900 (c) Johnson, M.; Arles, C.; Boons, G.-J. Tetrahedron Lett. 1998, 39, 9801-9804. (6) Izumi, M.; Ichikawa, Y. Tetrahedron Lett. 1998, 39, 2079-2082. (7) Wong, C.-H.; Ye, X.-S.; Zhang, Z. J. Am. Chem. Soc. 1998, 120, 7137-7138. (8) Takahashi, T.; Inoue, H.; Yamamura, Y.; Doi, T. Angew. Chem., Int. Ed. 2001, 40, 3230-3233. ORGANIC LETTERS 2002 Vol. 4, No. 24 4213-4216 10.1021/ol020150+ CCC: $22.00 © 2002 American Chemical Society Published on Web 10/30/2002