Thallium-containing Derivatives of Peptides

1,195,776. Thallium containing peptide derivatives. MERCK & CO. Inc. 28 June, 1968 [30 June, 1967], No. 30946/68. Headings C2C and C2J. Novel thallium and organo-thallium salts of peptide carbamates and thiocarbamates are prepared by the reaction of an N-carboxy- or thiocarboxy amino acid anhydride with an amino acid, a peptide or a functional derivative thereof in an aqueous medium in which said salts are insoluble under controlled conditions such that the only amino group present in appreciable concentration during the reaction is that in the starting amino acid or peptide, in which a thallous ion or an organothallic ion containing two C 1-10 organic radicals is present in the reaction mixture or is added after the completion of the coupling reaction. The salts may be converted to the corresponding peptides by addition of acid to the aqueous medium still containing the said salts. Organo thallium sulphonate salts used as the source of organothallium ions in the above process are prepared by the following sequence (R is a C 1-10 organic radical, e.g. alkyl, aryl, cycloalkyl, or heterocyclyl, X is Cl, Br or I, M is a metal which forms an insoluble chloride, bromide or iodide and R1 is the organic residue of a sulphonic acid, e.g. alkyl, hydroxyaryl, or aryl). Example 1 describes the preparation of dibutyl thallium methane sulphonate.