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

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 99m Tc (...

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Bibliographic Details
Published in:Synthesis (Stuttgart) 2009-03, Vol.2009 (5), p.787-792
Main Authors: Sparr, Christof, Michel, Urs, Marti, Roger E., Müller, Cristina, Schibli, Roger, Moser, Rudolf, Groehn, Viola
Format: Article
Language:English
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Summary: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 99m Tc (diagnosis) and ¹88 Re (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.
ISSN:0039-7881
1437-210X
DOI:10.1055/s-0028-1083345