Synthesis, Table of Contents SHORTPAPER © Georg Thieme Verlag Stuttgart · New York Efficient Synthesis of the Immunomodulating Compound KRP-203 Maiko Hamada*, Masatoshi Kiuchi, Kunitomo AdachiChemistry Laboratory Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, JapanFax: +81(45)9633529; e-Mail: Hamada.Maiko@mc.m-pharma.co.jp; Recommend Article Abstract Buy Article All articles of this category Abstract A practical and concise synthesis of KRP-203 (1) was achieved by utilizing a palladium coupling reaction mediated by XantPhos and Pd2(dba)3 as the key step. The coupling reaction of aryl bromide 5 with 3-hydroxythiophenol (6) proceeded chemoselectively to give phenol 7 in spite of the presence of a chlorine substituent on 5 and a hydroxyl group on 6. Phenol 7 was converted into KRP-203 by benzylation and removal of the protecting groups in high yield. Key words palladium - cross-coupling - synthesis - KRP-203 - FTY720 Full Text References References 1a Liu G. Link JT. Pei Z. Reilly EB. Leitza S. Nguyen B. Marsh KC. Okasinski GF. von Geldern TW. Ormes M. Fowler K. Gallatin M. J. Med. Chem. 2000, 43: 4025 1b Wang Y. Chackalamannil S. Chang W. Greenlee W. Ruperto V. Duffy RA. McQuade R. Lachowicz JE. Bioorg. Med. Chem. Lett. 2001, 11: 891 1c Bonnet B. Soullez D. Girault S. Maes L. Landry V. Davioud-Charvet E. Sergheraert C. Bioorg. Med. Chem. 2000, 8: 95 2 Pinchart A. Dallaire C. Gingras M. Tetrahedron Lett. 1998, 39: 543 3a Herradura PS. Pendola KA. Guy RK. Org. Lett. 2000, 2: 2019 3b Savarin C. Srogl J. Liebeskind LS. Org. Lett. 2002, 4: 4309 3c Bates CG. Gujadhur RK. Venkataraman D. Org. Lett. 2002, 4: 2803 3d Paloma C. Oiarbide M. López R. Gómez-Bengoa E. Tetrahedron Lett. 2000, 41: 1283 3e Kwong FY. Buchwald SL. Org. Lett. 2002, 4: 3517 3f Schopfer U. Schlapbach A. Tetrahedron 2001, 57: 3069 4 Shimizu H. Takahashi M. Kaneko T. Murakami T. Hakamata Y. Kudou S. Kishi T. Fukuchi K. Iwanami S. Kuriyama K. Yasue T. Enosawa S. Matsumoto K. Takeyoshi I. Morishita Y. Kobayashi E. Circulation 2005, 111: 222 5 Kiuchi M. Adachi K. Kohara T. Minoguchi M. Hanano T. Aoki Y. Mishina T. Arita M. Nakao N. Ohtsuki M. Hoshino Y. Teshima K. Chiba K. Sasaki S. Fujita T. J. Med. Chem. 2000, 43: 2946 6a Kahan BD. Karlix JL. Ferguson RM. Leichtman AB. Mulgaonkar S. Gonwa TA. Skerjanec A. Schmouder RL. Chodoff L. Transplantation 2003, 76: 1079 6b Tedesco-Silva H. Mourad G. Kahan BD. Boira JG. Weimar W. Mulgaonkar S. Nashan B. Madsen S. Charpentier B. Pellet P. Vanrenterghem Y. Transplantation 2004, 77: 1826 6c Kappos L. Antel J. Comi G. Montalban X. O’Connor P. Polman CH. Haas T. Korn AA. Karlsson G. Radue EW. N. Engl. J. Med. 2006, 355: 1124 7a Mandala S. Hadju R. Bergstrom J. Quackenbush E. Xie J. Milligan J. Thornton R. Shei G. Card D. Keohane C. Rosenbach M. Hale J. Lynch CL. Rupprecht K. Parsons W. Rosen H. Science 2002, 296: 346 7b Brinkmann V. Davis MD. Heise CE. Albert R. Cottens S. Hof R. Bruns C. Prieschl E. Baumruker T. Hiestand P. Foster CA. Zollinger M. Lynch KR. J. Biol. Chem. 2002, 277: 21453 8 Sanna MG. Liao J. Jo E. Alfonso C. Ahn M. Peterson MS. Webb B. Lefebvre S. Chun J. Gray N. Rosen H. J. Biol. Chem. 2004, 279: 13839 9 Fujishiro J. Kudou S. Iwai S. Takahashi M. Hakamata Y. Kinoshita M. Iwanami S. Izawa S. Yasue T. Hashizume K. Murakami T. Kobayashi E. Transplantation 2006, 82: 804 10a Konishi Y, Ando N, Kuriyama K, Iwanami S, and Kudou S. inventors; PCT Int. Appl. WO 03/029205. ; Chem. Abstr. 2003, 138, 304049 10b Tsubuki T, Kobayashi K, and Komatsu H. inventors; PCT Int. Appl. WO 2006/041019. ; Chem. Abstr. 2006, 144, 412416 11a Fan Y, Gao W, Gray N, Terding K, Lefebvre S, Mi Y, Nussbaumer P, Pan S, Wang W, Zecri F, Perez LB, La Montagne KR, and Ettmayer P. inventors; PCT Int. Appl. WO 03/099192. ; Chem. Abstr. 2003, 140, 4842 11b Kiuchi M, Kobayashi N, Sugahara K, and Nakamura M. inventors; PCT Int. Appl. WO 2006/129688. ; Chem. Abstr. 2006, 146, 45290 12 Itoh T. Mase T. Org. Lett. 2004, 6: 4587
