Synthesis 2009(5): 787-792  
DOI: 10.1055/s-0028-1083345
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a Novel γ-Folic Acid-N τ-Histidine Conjugate Suitable for Labeling with 99mTc and 188Re

Christof Sparra, Urs Michela, Roger E. Martia, Cristina Müllerb, Roger Schiblib, Rudolf Moserc, Viola Groehn*c
a School of Life Sciences and Facility Management, Institute for Chemistry and Biological Chemistry, Zurich University of Applied Sciences, Grüental, 8820 Wädenswil, Switzerland
b Paul Scherrer Institute, Center for Radiopharmaceutical Science, OIPA, 5232 Villigen PSI, Switzerland
c Merck Eprova AG, Im Laternenacker 5, 8200 Schaffhausen, Switzerland
Fax: +41(52)6307255; e-Mail: [email protected];
Further Information

Publication History

Received 7 October 2008
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.

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