Synthesis of a Novel gamma-Folic Acid-N-tau-Histidine Conjugate Suitable for Labeling with Tc-99m and Re-188

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 gamma-folic acid-N-tau-histidine conjugate 1 wherein the N-tau-histidine is suitable for radiolabeling with isotopes Tc-99m (dia...

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Bibliographic Details
Published inSynthesis (Stuttgart) no. 5; pp. 787 - 792
Main Authors Sparr, Christof, Michel, Urs, Marti, Roger E., Mueller, Cristina, Schibli, Roger, Moser, Rudolf, Groehn, Viola
Format Journal Article
LanguageEnglish
Published STUTTGART Thieme Medical Publishers 02.03.2009
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
regioselectivity
AGENT
CHAIN
receptor
alkylations
amino acids
OVARIAN-CANCER
NORMAL-TISSUES
organometallic
REGIOSPECIFIC ALKYLATION
FOLATE
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Summary: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 gamma-folic acid-N-tau-histidine conjugate 1 wherein the N-tau-histidine is suitable for radiolabeling with isotopes Tc-99m (diagnosis) and Re-188 (therapy). A modular synthetic strategy was applied: N-alpha-Boc-alpha-carboxy-protected glutamic acid was amidically linked to N-tau-functionalized amino-alkyl)histidine via the gamma-carboxy group to form building block 8. Intermediate 8 was coupled to protected pteroic acid to give I in two steps in 47% yield. N-tau-(Functionalized aminoalkyl)histidine was synthesized by two different routes. The preferred route starting from Boc-His-OMe led in two steps to the N-tau-(functionalized aminoalkyl)histidine in 36% yield.
ISSN:0039-7881
1437-210X
DOI:10.1055/s-0028-1083345