Traumatic Shock. Ii. the Preparation of Cystine, Methionine, and Homocystine Containing Radioactive Sulfur.

In order to prepare, from radioactive sulfur, the sulfur-containing amino acids of a high order of specific activity for biological experiments such as those described in the foregoing publication, it was necessary (owing to the cost of radioactive sulfur) to investigate the efficiency of utilization of small amounts of sulfur. The synthetic methods utilized are not novel, but are described below because of the data obtained on yields in numerous small scale preparations. Since present methods of preparing radioactive sulfur from neutron bombardment of carbon tetrachloride involve its isolation and purification as BaSO, (1), the schema of synthesis used for the preparation of three sulfur containing amino acids begins with barium sulfate (Figure 1). The synthesis of radioactive methionine (VI) from radioactive sulfur (0.05 moles) was reported by Tarver and Schmidt (2), using a modification of the synthesis of homocystine (V) reported by Patterson and du Vigneaud (3). The same yields as they report were obtained in preparing homocystine from 0.06 moles of sulfur. However , in the methylation of homocysteine, we were unable to obtain the anticipated yields. It was found that for preparing homocystine, the more convenient reduction of benzylhomocysteine (IV) with sodium and butyl alcohol gave as good yields as reduction with sodium and liquid ammonia. For the preparation of methionine, treatment of the resultant sodium salt of homocysteine with methyl iodide did not give as good yields as reported by Tarver and Schmidt, whether reduction was conducted in liquid ammonia or butyl alcohol. Attempted methylation with dimethyl sulfate and diazomethane did not proceed well. The method of synthesis of cystine (IX) from 1 Part of this work was done in partial fulfillment of the Bachelor's Degree with honors in biochemistry, Har-vard University. benzyl mercaptan (I) (0.6 moles), reported by Wood and du Vigneaud (4) in 23 per cent yield, was found to give a 21.5 per cent yield when 0.06 mole was used. Reduction of benzylcysteine (VIII) to cysteine with sodium and butyl alcohol did not give good yields; therefore, sodium and liquid ammonia were used. Since radioactive benzyl mercaptan is necessary for the synthesis of all three amino acids, a method of preparation of the mercaptan from hydrogen sulfide, other than that described by Tarver and Schmidt, in 70 per cent yield, was investigated. Elementary sulfur was prepared from hydrogen sulfide by oxidation with iodine, and this was treated with benzylmag-nesium chloride. The yield of …