Synthesis of a Photo‐Caged DOPA Derivative by Selective Alkylation of 3,4‐Dihydroxybenzaldehyde

Abstract

Natural and synthetic polymers containing the catechol moiety of noncoded amino acid 3,4‐dihydroxyphenylalanine (DOPA) are capable of metal‐coordination and adhesion under wet conditions. Masking the catechol subunit with a photo‐cleavable group would provide an opportunity to design tunable adhesion properties that are especially important for biomaterial and biomedicine applications. Herein, we report the regioselective synthesis of a photo‐caged DOPA bearing an ortho‐nitrobenzyl (oNB) group that is capable of undergoing cleavage upon irradiation with UV light. We developed a selective synthetic route towards a 3‐O‐oNB alkylated DOPA regioisomer that can be readily incorporated into proteins by using a previously developed bio‐expression platform. The synthesis is based on a regioselectivity switch in 3,4‐dihydrozybenzaldehyde alkylation upon application of different equivalents of deprotonating base. The enantiomerically pure 3‐O‐oNB‐DOPA was prepared on a gram scale and proved to be generally compatible with the solid‐phase peptide synthesis conditions. We also demonstrate the general applicability of the developed synthetic strategy by providing the synthesis of 3‐O‐methyl‐DOPA.

Adhesive Materials Inspired by Barnacle Underwater Adhesion: Biological Principles and Biomimetic Designs

“…Owing to these properties, the authors suggested that this adhesive material is well suited for the repair of tendon-to-bone injuries. Taking advantage of the genetic code expansion technology can not only high efficiently introduce Dopa functionality but also engineer UV-responsive smart adhesives by incorporating photocaged Dopa derivatives ( Hauf et al, 2017 ; Schneider et al, 2017 ; Schneider et al, 2018 ).…”

Chromium–Salen Complex/Nitroxyl Radical Cooperative Catalysis: A Combination for Aerobic Intramolecular Dearomative Coupling of Phenols

“…Characterization data were in agreement with previously reported values. 29 (4-((tert-Butyldimethylsilyl)oxy)-3-methoxyphenyl)methanol (S25). To a solution of aldehyde S24 (1.96 g, 7.5 mmol) in MeOH (23 mL) was added NaBH 4 (318 mg, 9.0 mmol) at 0 °C.…”

“…Characterization data were in agreement with previously reported values. 29 (4-(Bromomethyl)-2-methoxyphenoxy)(tert-butyl)dimethylsilane (S26). To a solution of alcohol S25 (1.07 g, 4.0 mmol) in CH 2 Cl 2 (12 mL) was added PBr 3 (0.30 mL, 3.2 mmol) slowly at 0 °C.…”

“…Characterization data were in agreement with previously reported values. 29 The Journal of Organic Chemistry (4-((tert-Butyldimethylsilyl)oxy)-3-methoxybenzyl) Ethanethioate (S27). To a solution of bromide S26 (331 mg, 1.0 mmol) in DMF (3 mL) was added AcSK (137 mg, 1.2 mmol) at room temperature.…”

Development of a synthetic equivalent of α,α-dicationic acetic acid leading to unnatural amino acid derivatives via tetrafunctionalized methanes

“…15 A combination of methods b and c , referred as the Bucherer–Bergs reaction, also furnishes 5,5-disubstituted hydantoins. 16 In contrast, our synthetic method (method d ) achieved the synthesis of amino acid derivatives by decarboxylation 17 of α,α-disubstituted malonate, in which the α-substituent is easily modified by altering the nucleophile. Because α,α-disubstituted malonate has multiple coordination sites, control of stereochemistry is expected to be easier than methods a–c .…”