1. (1-Beta-mercaptopropionic acid, 2-(3,5-dibromo-L-tyrosine))oxytocin, a potent inhibitor of oxytocin
E O Lundell, M F Ferger J Med Chem. 1975 Oct;18(10):1045-7. doi: 10.1021/jm00244a023.
[1-Beta-Mercaptopropionic acid,2-(3,5-dibromo-L-tyrosine)]oxytocin was synthesized from a protected polypeptide intermediate that had been prepared by the condensation of S-ethylcarbamoyl-beta-mercaptopropionyl-3,5-dibromotyrosine with H-Ile-Gln-Asn-Cys(Ec)-Pro-Leu-Gly-NH2, using dicyclohexylcarbodiimide in dimethylformamide. The ethylcarbamoyl (Ec) protecting groups were removed by refluxing NH3, and the resulting disulfhydryl peptide was oxidatively cyclized to the corresponding disulfide by ICH2CH2I. Purification of the analog was effected by partition chromatography and gel filtration. The analog possesses antioxytocic (pA2 = 7.05) and antiavian vasodepressor (pA2 = 7.44) activities but has neither agonist nor antagonist activity in the rat pressor assay.
2. N-Acetyl-3,5-dibromo-l-tyrosine hemihydrate
Pakorn Bovonsombat, John Snyder, Francesco Caruso, Miriam Rossi Acta Crystallogr Sect E Struct Rep Online. 2012 Sep 1;68(Pt 9):o2601-2. doi: 10.1107/S1600536812032928. Epub 2012 Aug 1.
The title compound, C(11)H(11)Br(2)NO(4)·0.5H(2)O, was prepared by an electrophilic bromination of N-acetyl-l-tyrosine in acetonitrile at room temperature. The two independent mol-ecules do not differ substanti-ally and a mol-ecule of water completes the asymmetric unit. The synthesis of the title compound does not modify the stereochemical center, as shown by the absolute configuration found in this crystal structure. Comparison with the non-bromo starting material differs mainly by rotation features. For instance the H(methine)-C(chiral center)-C(methyl-ene)-C(ipso) is 173.0 (2)° torsion angle in one mol-ecule and 177.3 (2)° in the other, indicating a trans arrangement. This is in contrast with approximately 50° in the starting material. A short inter-molecular Br⋯Br separation is observed [3.2938 (3) Å]. The molecules in the crystal are connected via a network of hydrogen bonds through an N-H⋯O hydrogen bond between the hydroxy group of the phenol of the tyrosine and the N-H of the amide of the other molecule and an O-H⋯O hydrogen bond between the hydroxy group of the carboxylic acid and the oxygen of the carbonyl of the amide.
3. Preparation of 3-bromo-L-tyrosine and 3,5-dibromo-L-tyrosine
Robert S Phillips, Susan Busby, Leia Edenfield, Kevin Wickware Amino Acids. 2013 Feb;44(2):529-32. doi: 10.1007/s00726-012-1366-z. Epub 2012 Jul 27.
L-Tyrosine is converted to 3-bromo-L-tyrosine in good yield by reaction with 1.2 equiv. of DMSO in HBr/AcOH, while reaction with 2.2 equiv. of DMSO under comparable conditions results in formation of 3,5-dibromo-L-tyrosine in good yield. This is the simplest, safest and most efficient method for the preparation of gram quantities of either 3-bromo-L-tyrosine or 3,5-dibromo-L-tyrosine.
