Angiotensin-II Analogues. I: Synthesis and incorporation of the halogenated amino acids 3-(4′-iodophenyl)alanine, 3-(3′,5′-dibromo-4′-chlorophenyl)alanine, 3-(3′,4′,5′-tribromophenyl)alanine, and 3-(2′,3′,4′,5′,6′-pentabromophenyl)alanine

✍ Scribed by Richard Leduc; Michel Bernier; Emanuel Escher

• Publisher: John Wiley and Sons
• Year: 1983
• Tongue: German
• Weight: 735 KB
• Volume: 66
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19830660329

✦ Synopsis

Abstract

The synthesis of the polyhalogenated phenylalanines Phe(3′,4′,5′‐Br~3~) (3), Phe(3′,5′‐Br~2~‐4′‐Cl) (4) and DL‐Phe (2′,3′,4′,5′,6′‐Br~5~) (9) is described. The trihalogenated phenylalanines 3 and 4 are obtained stereospecifically from Phe(4′‐NH~2~) by electrophilic bromination followed by Sandmeyer reaction. The most hydrophobic amino acid 9 is synthesized from pentabromobenzyl bromide and a glycine analogue by phase‐transfer catalysis. With the amino acids 4, 9, Phe(4′‐I) and D‐Phe, analogues of [1‐sarcosin]angiotensin II ([Sar^1^]AT) are produced for structure‐activity studies and tritium incorporation. The diastereomeric pentabromo peptides L‐ and D‐13 are separated by HPLC. and identified by catalytic dehalogenation and comparison to [Sar^1^]AT (10) and [Sar^1^, D‐Phe^8^]AT (14).