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Amino Acids (2013) 44:529532 DOI 10.1007/s00726-012-1366-z
ORIGINAL ARTICLE
Preparation of 3-bromo-L-tyrosine and 3,5-dibromo-L-tyrosine
Robert S. Phillips Susan Busby Leia Edeneld
Kevin Wickware
Received: 7 May 2012 / Accepted: 10 July 2012 / Published online: 27 July 2012 Springer-Verlag 2012
Abstract 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 efcient method for the preparation of gram quantities of either 3-bromo-L-tyrosine or 3,5-dibromo-L-tyrosine.
Keywords Bromination Bromotyrosine
Dibromotyrosine DMSO/HBr Tyrosine
AbbreviationsDMSO Dimethyl sulfoxide AcOH Acetic acid
Introduction
3-Bromo-L-tyrosine and 3,5-dibromo-L-tyrosine are common metabolites of L-tyrosine in marine organisms, particularly in sponges, and they serve as the basic structural element for an important class of marine bromotyrosine
alkaloids, with potent antimicrobial, antitumor and anti-malarial activities (Yin et al. 2011; Xu et al. 2011; Kon et al. 2010; Mukai et al. 2009). Examples of 3,5-dibromotyrosine-derived alkaloids include pseudoceramine A (1) (Yin et al. 2011), psammaplysin H (2) (Xu et al. 2011), and ceratinadin A (3) (Kon et al. 2010) which are shown in Scheme 1. Thus, 3-bromo-L-tyrosine and 3,5-dibromo-L-tyrosine are useful intermediates in the synthesis of some of these alkaloids. Furthermore, 3-bromo-L-tyrosine and 3,5-dibromo-L-tyrosine are produced by the action of myeloperoxidase in humans, and serve as markers in urine for immune stimulation and oxidative stress (Wu et al. 1999; Senthilmohan and Kettle 2006). However, there are relatively few synthesis of 3-bromo-L-tyrosine reported in the literature, and none of them are particularly convenient and efcient for multigram-scale preparation. In conjunction with our mechanistic studies of tyrosine phenol-lyase (Phillips et al. 2006), we required samples of pure 3-bromo-L-tyrosine. Furthermore, we were interested whether 3-bromo-L-tyrosine and 3,5-dibromo-L-tyrosine produced in vivo by oxidative stress (Wu et al. 1999; Senthilmohan and Kettle 2006) may be substrates or inhibitors of human DOPA decarboxylase.
Methods
3-Bromo-L-tyrosine (4)
L-Tyrosine (5.0 g, 27.6 mmol) was suspended in 50 mL AcOH, and 12 mL 48 % HBr (108 mmol) was added. Then, 2.4 mL DMSO (33.1 mmol) was added, and the colorless suspension immediately turned yelloworange. The suspension was warmed to 65 C for 2 h, giving a clear light yellow solution. It was...