Phenol → HCID 68637794, compound

Participants

Reaction Steps

The synthesis of the fluorescein precursor compound 18 is shown in Scheme 5. The xanthene half of 18 was synthesized from the xanthone precursor 7. The latter was prepared via the Friedel-Crafts acylation of 342 with 6. The product was subsequently heated in a sealed tube to furnish the xanthone 8 and the phenol moieties then protected as 2-methoxyethoxymethyl (MEM)43 ethers (9). The aromatic precursor (13) to the “northern” half of compound 18 was prepared in three steps from commercially available o-aminophenol (described above). Compound 13 contains a doubly protected iminodiacetic acid moiety and a benzylated phenol. The latter will ultimately be debenzylated so that it can serve as the attachment site for the peptide. Compound 13 was lithiated at −105° C. and coupled to 9, to furnish adduct 14 in 69% yield. The benzylated phenol in 14 was transformed in three steps to the desired carboxylic acid (18), and then coupled to H2N-Ser(O-tBu)-Phe-[(Arg)Mtr]4-resin (prepared via standard Fmoc solid phase peptide synthesis on the Rink resin). Finally, exposure of the resin-appended fluorophore-peptide to 95% CF3CO2H resulted in the simultaneous cleavage of the peptide from the resin, MEM ether deprotection, and complete aromatization of the tricyclic nucleus via loss of the tertiary hydroxyl moiety to yield 23.

Provenance & Evidence