Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Synthesis 2007(13): 1927-1929
DOI: 10.1055/s-2007-983721
DOI: 10.1055/s-2007-983721
SHORTPAPER
© Georg Thieme Verlag Stuttgart · New York
Efficient Synthesis of the Immunomodulating Compound KRP-203
Further Information
Received
6 March 2007
Publication Date:
18 June 2007 (online)
Publication History
Publication Date:
18 June 2007 (online)
![](https://www.thieme-connect.de/media/synthesis/200713/lookinside/thumbnails/10.1055-s-2007-983721-1.jpg)
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
-
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, andKudou S. inventors; PCT Int. Appl. WO 03/029205. ; Chem. Abstr. 2003, 138, 304049 -
10b
Tsubuki T,Kobayashi K, andKomatsu 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, andEttmayer P. inventors; PCT Int. Appl. WO 03/099192. ; Chem. Abstr. 2003, 140, 4842 -
11b
Kiuchi M,Kobayashi N,Sugahara K, andNakamura M. inventors; PCT Int. Appl. WO 2006/129688. ; Chem. Abstr. 2006, 146, 45290 - 12
Itoh T.Mase T. Org. Lett. 2004, 6: 4587