Synthesis and characterization of Four-functional fluoresceins

• Published in: Journal of molecular liquids 2023-07, Vol.381, p.121747, Article 121747
• Main Authors: Puskas, Judit E., Shrikhande, Gayatri, Molnar, Kristof
• Format: Article
• Language: English
• Subjects: Candida antarctica Lipase B; Enyzme catalysis; Fluoresceins; Michael addition
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2023.121747

[Display omitted] •Efficient scaled-up synthesis of fluorescein diacrylate was achieved.•Michael addition of diallylamine to fluorescein-diacrylate was instantaneous.•Enzyme catalysis was used for Michael addition of amines with ester and hydroxy functionalities to fluorescein-diacrylate.•NMR spectroscopy and high-resolution mass spectrometry was used to verify the structure and purity of the products.•Multifunctional fluoresceins are good candidates for the synthesis of imaging agents for a wide variety of applications. The synthesis of fluorescein-diacrylate (FL-DA) and four-functional fluoresceins (FL) by Michael addition of secondary amines to FL-DA was investigated. FL-DA was successfully synthesized at the ∼ 100 g level. Diallyl amine (DAA) reacted with FL-DA instantaneously. Diethanolamine (DEA) also reacted within 5 min but was unstable and hydrolyzed back to FL. Michael addition of aminodiols with longer carbon chains and diethyl-amino-diacetate (DIDA) was slower but could be accelerated using Candida antarctica lipase B (CALB) as a biocatalyst. The structure of tetrafunctional fluorosceins was confirmed by 13C and 1H NMR. High resolution Mass Spectrometry (HRMS) demonstrated the formation of very pure tetraallyl- and tetraethylacetate-fluoresceins. These multifuntional fluoresceins are good candidates for the synthesis of imaging agents for a wide variety of applications.