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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)
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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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