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Synthesis of a Photo‐Caged DOPA Derivative by Selective Alkylation of 3,4‐Dihydroxybenzaldehyde
Author(s) -
Schneider Tobias,
Kubyshkin Vladimir,
Budisa Nediljko
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201701749
Subject(s) - chemistry , regioselectivity , alkylation , moiety , combinatorial chemistry , catechol , solid phase synthesis , thiophosphate , peptide , organic chemistry , catalysis , biochemistry
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 ( o NB) group that is capable of undergoing cleavage upon irradiation with UV light. We developed a selective synthetic route towards a 3‐ O ‐ o NB 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 ‐ o NB‐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.