US EPA

7547586 

Journal Article 

Total Synthesis of L,L-Isodityrosine and Isodityrosine-Derived Agents: K-13, OF4949-III, and OF4949-IV 

Boger, DL; Yohannes, D 

1990 

Yes 

Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904 

AMER CHEMICAL SOC 

WASHINGTON 

55 

24 

6000-6017 

English 

10.1021/jo00311a019 

WOS:A1990EK03200019 

Full details of the development of reaction conditions for implementation of an activated Ullmann condensation reaction that may be conducted without amino acid racemization and that have proven suitable for incorporation of the selectively protected catechol of functionalized L-Dopa derivatives are described. The application of this procedure in the total synthesis of L,L-isodityrosine (15), K-13 (1), and OF4949-III/OF4949TV (4/5) is detailed. Full details of a study of the macrocyclization reaction required for formation of the 17-membered tripeptides incorporating a diaryl ether linked meta- and paracyclophane structural subunit are provided and illustrate that the cyclization in route to K-13/OF4949-I - OF4949-IV is optimally conducted on substrates bearing a carbamate derivative of the C-15/C-9 amine and a C-4 free phenol with C11-N10/C10-N11 amide bond closure. © 1990, American Chemical Society. All rights reserved. 

amino acid derivative; enzyme inhibitor; isodityrosine; k 13; of 4949 iii; of 4949 iv; peptide; unclassified drug; article; drug structure; drug synthesis; reaction analysis