Development of a Visible Light Triggerable Traceless Staudinger Ligation Reagent

• Published in: Journal of organic chemistry Vol. 83; no. 21; pp. 12998 - 13010
• Main Authors: Hu, Peng, Berning, Karsten, Lam, Yun-Wah, Ng, Isabel Hei-Ma, Yeung, Chi-Chung, Lam, Michael Hon-Wah
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 02.11.2018; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; CELLS; PHOTOCLICK CHEMISTRY; CLICK REACTIONS; ACTINOMETER; SURFACE; FERRIOXALATE; BERTOZZI LIGATION; AZIDE; PEPTIDE; IMMOBILIZATION
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.8b01370

A series of substituted 9-methylenylanthracene photocages for diphenylphosphinothioesters have been synthesized to explore their photo-uncaging properties by visible light. Substituents such as phenyl, p-trifluoromethylphenyl, p-methoxyphenyl, ethyn-1-ylbenzene, and 3,3-dimethylbut-1-yn-1-yl have been introduced in order to extend the π-conjugation of the photocage and to shift the wavelength response of the uncaging process to the visible spectral range. Among these new photocages, the (10-(3,3-dimethylbut-1-yn-1-yl)­anthracen-9-yl)­methyl has been shown to have the best performance in terms of fast photo-uncaging and minimal byproduct formation. It is responsive to both UV and visible photoexcitation. Quantum yields of the photoinduced heterolytic anthracenylmethyl–phosphorus bond cleavage at 366 and 416 nm were found to be 0.08 and 0.025, respectively. This photocage enables traceless Staudinger ligation to be triggered by photoirradiation in the visible spectral range for bioconjugation applications. We demonstrate this with a series of visible-light-induced oligopeptide syntheses via the conjugation of amino acid/oligopeptide building blocks by the characteristic peptide linkage attained by traceless Staudinger ligation. Yields of the resultant conjugated oligopeptides ranged from 31 to 43%. This new photocage opens up the possibility of in situ synthesis of functional proteins/peptides mediated by visible-light-induced photoclick processes for the regulation of cellular/metabolic functions of life systems.