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. Author manuscript; available in PMC: 2019 Aug 25.
Published in final edited form as: Nat Chem. 2019 Feb 25;11(4):335–341. doi: 10.1038/s41557-019-0217-x

Figure 1. Synthetic routes for preparation of the RfDAAs.

Figure 1.

Each synthetic route utilized an alkylated tetrahydroquinoline core structure (1) that incorporated an ester group to provide a functional handle for subsequent D-amino acid coupling. After Vilsmeier-Haack formylation, condensation with t-butyl cyanoacetate provided the fluorogenic fluorophore, Rf420 (3), which was coupled with D-Lys to generate Rf420DL. A similar strategy was used to prepare Rf470DL. A thiophene spacer, installed via iodination of the aryl ring and a subsequent Suzuki-Miyaura coupling reaction, was added to the tetrahydroquinoline core in order to further extend conjugation (e.g., 6). Rf490DL, a constitutional isomer of Rf470DL, was prepared by coupling D-Lys to the deprotected α-cyanoacrylic acid subunit (7).