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Synlett 2012(2): 306-310  
DOI: 10.1055/s-0031-1290139
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Development of a Near Infrared Fluorescence Labeling Reagent: Synthesis of Indole-Functionalized Indocyanine Green Derivatives

Takayuki Doi*a, Koya Oikawaa, Jun Suzukia, Masahito Yoshidaa, Nobuhiko Ikib
a Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan
Fax: +81(22)7956864; e-Mail: doi_taka@mail.pharm.tohoku.ac.jp;
b Graduate School of Environmental Studies, Tohoku University, 6-6-07 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan
Further Information

Publication History

Received 9 September 2011
Publication Date:
03 January 2012 (online)

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Abstract

We have demonstrated a facile synthesis of functionalized indocyanine green (ICG) derivatives. Heteroatom-substituted indolenine was synthesized via SNAr reaction of 5-chloro-2,4-di­nitroanisole with 1,2-dimethyl-1-propenyl trimethylsilyl ether followed by reduction of the nitro groups. After the introduction of hydrophilic butanesulfonate moieties, homo- and heterocondensations with glutaconaldehyde dianilide provided symmetrical and unsymmetrical ICG derivatives, which exhibit near infrared (NIR) absorption and fluorescence emission similar to those of ICG. NIR fluorescence labeling reagent was synthesized using the amino group in the ICG derivative. The 1,3-dipolar cycloaddition with benzyl azide was performed utilizing copper nanoparticles toward a versatile method for the synthesis of NIR molecular imaging probes.

Key words

cycloaddition - indoles - nucleophilic aromatic substitution - indocyanine green - near infrared fluorescence

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