A Practical Synthesis of 6,8-Difluoro-7-hydroxycoumarin Derivatives for Fluorescence Applications

作者：Kerkovius Jeff K; Menard Frederic

来源：Synthesis (Germany), 2016, 48(11): 1622-1629.

DOI：10.1055/s-0035-1561603

• fluorinated coumarin dyes
• fluorinated coumaric acid
• fluorescent dye
• imaging probe
• NHS ester

A practical synthesis for 6,8-difluoro-7-hydroxycoumarin-3-carboxylic acid - one of the most widely used coumarin fluorescence imaging dye for bioconjugation - is reported. The synthesis was optimized for a preparative scale to obtain 14 g of the fluorescent coumaryl acid, 6,8-difluoro-7-hydroxycoumarin-3-carboxylic acid. Using this sequence, the preparation of its NHS ester requires a single chromatographic separation for a total of eight synthetic steps. Coupling of the key coumaryl NHS ester is also demonstrated with an unprotected hydroxyamine linker chain for further derivatization. This report provides a convenient access to the fluorinated dye for research labs as an alternative to currently cost-prohibitive commercial sources.

• 出版日期2016-6