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DOI: 10.1055/s-0028-1083345
Synthesis of a Novel γ-Folic Acid-N τ-Histidine Conjugate Suitable for Labeling with 99mTc and 188Re
Publication History
Publication Date:
27 January 2009 (online)
Abstract
Radiolabeled folate derivatives have the potential to target folate receptor-positive tumor cells for noninvasive diagnosis and therapy. We report the synthesis of a novel γ-folic acid-N τ-histidine conjugate 1 wherein the N τ-histidine is suitable for radiolabeling with isotopes 99mTc (diagnosis) and ¹88Re (therapy). A modular synthetic strategy was applied: N α-Boc-α-carboxy-protected glutamic acid was amidically linked to N τ-(functionalized aminoalkyl)histidine via the γ-carboxy group to form building block 8. Intermediate 8 was coupled to protected pteroic acid to give 1 in two steps in 47% yield. N τ-(Functionalized aminoalkyl)histidine was synthesized by two different routes. The preferred route starting from Boc-His-OMe led in two steps to the N τ-(functionalized aminoalkyl)histidine in 36% yield.
Key words
alkylations - amino acids - regioselectivity - organometallic - receptor
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1a
Weitmann SD.Lark RH.Coney LR.Fort DW.Frasca V.Zurawski VR. Cancer Res. 1991, 52: 3396 -
1b
Parker N.Turk MJ.Westrick E.Lewis JD.Low PS.Leamon CP. Anal. Biochem. 2005, 338: 284 - 2
Leamon CP.Reddy JA. Adv. Drug Delivery Rev. 2004, 56: 1127 - 3
Li S.Deshmukh HM.Huang L. Pharm. Res. 1998, 15: 1540 - 4
Cho BK.Roy EJ.Patrick TA.Kranz DM. Bioconjugate Chem. 1997, 8: 338 - 5
Leamon CP.Pastan I.Low PS. J. Biol. Chem. 1993, 268: 24847 - 6
Gabizon A.Shmeeda H.Horowitz AT.Zalipsky S. Adv. Drug. Delivery Rev. 2004, 56: 1177 -
7a
Mathias CJ.Lewis MR.Reichert DE.Laforest R.Sharp TL.Lewis JS. Nucl. Med. Biol. 2003, 30: 725 -
7b
Mathias CJ.Wang S.Lee RJ.Waters DJ.Low PS.Green MA. J. Nucl. Med. 1996, 37: 1003 -
7c
Mathias CJ.Wang S.Low PS.Waters DJ.Green MA. J. Nucl. Med. 1999, 26: 23 -
7d
Mathias CJ.Green MA. Nucl. Med. Biol. 1998, 25: 585 -
7e
Mathias CJ.Green MA. J. Nucl. Med. 2000, 41: 1113 -
7f
Siegel BA.Dehdashti F.Mutch DG.Podoloff DA.Wendt R.Sutton GP. J. Nucl. Med. 2003, 44: 700 -
7g
Guo W.Hinkle G.Lee R. J. Nucl. Med. 1999, 40: 1563 -
7h
Reddy JA.Xu LC.Parker N.Vetzel M.Leamon CP. J. Nucl. Med. 2004, 45: 857 - 8
Müller C.Schubiger PA.Schibli R. Nucl. Med. Biol. 2007, 34: 595 -
9a
Müller C.Schubiger PA.Schibli R. Eur. J. Nucl. Med. Mol. Imaging 2006, 33: 1162 -
9b
Müller C.Dumas C.Hoffmann U.Schubiger PA.Schibli R. J. Organomet. Chem. 2004, 689: 4712 -
9c
Müller C.Schubiger PA.Schibli R. Bioconjugate Chem. 2006, 17: 797 - 10
van Staveren DR.Waibel R.Mundwiler S.Schubiger PA.Alberto R. J. Organomet. Chem. 2004, 689: 4803 -
11a
Bell JR.Jones JH. J. Chem. Soc., Perkin Trans. 1 1974, 2336 -
11b
Fletcher AR.Jones JH.Ramage WI.Stachulski AV. J. Chem. Soc., Perkin Trans. 1 1979, 2261 -
11c
Brown T.Jones JH.Wallis JD. J. Chem. Soc., Perkin Trans. 1 1982, 3045 -
11d
Chivikas CJ.Hodges JC. J. Org. Chem. 1987, 52: 3591 -
11e
Hodges JC. Synthesis 1987, 20 -
11f
Nayak SK.Monga V.Kaur N.Jain R. J. Heterocycl. Chem. 2007, 44: 1265 -
11g
Kaur N.Monga V.Jain R. Tetrahedron Lett. 2004, 45: 6883 -
12a
Jones JH.Rathbone DL.Wyatt PB. Synthesis 1987, 1110 -
12b
Aurelio L.Brownlee RTC.Hughes AB. Org. Lett. 2002, 4: 3767 - 13
Yao L.Smith BT.Aubé J. J. Org. Chem. 2004, 69: 1720 -
14a
Jain R.Cohen LA. Tetrahedron 1996, 52: 5363 -
14b
Guillen F.Bregon D.Plaquevent JC. Tetrahedron Lett. 2006, 47: 1245 - 15
Bodanszky A.Bodanszky M.Chandramouli N.Kwei JZ.Martinez J.Tolle JC. J. Org. Chem. 1980, 45: 72 - 16
Kunishima M.Kawachi C.Morita J.Terao K.Iwasaki F.Tani S. Tetrahedron 1999, 55: 13159 - 17
Taylor EC.Young WB. J. Org. Chem. 1995, 60: 7947 - 18
Müller C.Forrer F.Schibli R.Krenning EP.de Jong M. J. Nucl. Med. 2008, 49: 310 - 19
Alberto R.Ortner K.Wheatley N.Schibli R.Schubiger AP. J. Am. Chem. Soc. 2001, 123: 3135