Selenotyrosine and related phenylalanine derivatives

A new series of Se-substituted phenylalanine derivatives has been synthesized having the para position of the phenyl ring substituted by selenocyanate (-SeCN), seleninic acid (-SeO2H), or selenol (-SeH) functional groups. The starting material for synthesis was 4'-aminophenylalanine, which is readily available in DL- or L- forms. Selenium was incorporated into the ring by reacting the unprotected amino acid with nitrous acid, followed by reaction of the diazotized aromatic amine with potassium selenocyanate at pH 4-5 to give phenylalanine selenocyanate. The selenocyanate derivative was converted to the selenol directly by reduction with sodium borohydride, or oxidized to the seleninic acid, which was then reduced to the selenol. Alkylation of the selenol ('selenotyrosine') gave the selenoether derivatives of phenylalanine [(Phe-SeR), R = methyl or allyl], and air oxidation of the selenol gave the diselenide. Mild oxidation of the selenoether 4'-(MeSe)Phe with peroxide gave the selenoxide derivative, 4'[Se(O)Me]. Because of their stability and useful redox properties, aromatic selenoamino acids can be used as synthetic analogues to increase chemical functionality in proteins or peptides, and have potential pharmaceutical or nutritional applications. The possibility that aromatic selenoamino acids could be formed metabolically through reactions of reactive selenium intermediates with aromatic amino acid residues is discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.