Diary1 ethers of tyrosine, maintaining optical activity, have been formed through the reaction of a Abstract: tyrosine derivative with an aryl iodonium salt.
Of late, there has been an increased interest in the glycopeptide class of antibiotics because of their activity against multiple resistant Stauhvlococcus ameus (MRSA)'. This interest has been reflected by a vastly expanded number of reports of new glycopeptides whose structures, while they vary markedly in substitution, all contain the polycyclic heptapeptide core of vancomycin ( 1)2. The phenolically linked amino acid residues, either as biphenyls or as diary1 ethers, constitute an unusual feature of the structure and presumably are involved in the maintenance of conformational ridigity. Recently, two other natural products, OF 4949 (2)3, and K134, have been isolated which also contain tyrosine residues which are linked in a ring as a diary1 ether.
We report here an approach to ethers related to these natural products.
OMe
The classical and most widely used synthesis of diphenyl ethers, the Ulhnann reaction5, requires forcing conditions not compatible with amino acids containing base-or heat-sensitive functionality. This problem led Hamilton6 to adopt a method involving displacement, by phenolate (or phenoxide), of a tosylate from an activated dinitro-tyrosine derivative. Evans7 has tackled the formation of the diethers of tyrosine by using the Ullmann reaction to yield diphenyl ethers priorto the construction of amino acid side chains. Recently, however, Boger and Yohannes* have developed conditions for the Ullmann condensation giving coupled products without amino acid racemisation. In a related approach Pearson9 chose to use an atyl manganese complex to facilitate activation, while Still1o has prepared similar thioethers by a photochemical Sml reaction.