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

Christof Sparr; Urs Michel; Roger E. Marti; Cristina Müller; Roger Schibli; Rudolf Moser; Viola Groehn

doi:10.1055/s-0028-1083345

PAPER

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

Christof Sparr^a, Urs Michel^a, Roger E. Marti^a, Cristina Müller^b, Roger Schibli^b, Rudolf Moser^c, 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: viola.groehn@eprova.com;

Abstract

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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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References

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

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