SIDNEY W. Fox
194 [CONTRIBUTION FROM
THE
Vol. 68
CHEMISTRY DEPARTMENT, IOWA STATE COLLEGE]
Amino Acid Conversion Products. 111. 3,5-Diiodotyrosine Derivatives BY SIDNEY W. Fox Since diiodotyrosine may be prepared from one ethanol a sample decomposed a t 215-216' (uncor.) with 0.2" when 0.775 g. and had [aID1,+18.7 of the amino acids which is available in quantity, prebrowning was made up to 10.0 cc. with 9570 ethanol. the possible synthesis of radio-opaque derivatives The mother liquor of the original precipitate was conis of interest. The structurally related com- centrated to dryness, the residue dissolved in 70 cc. of hot pound, /3-(4-hydroxy-3,5-diiodophenyl)-a-phenyl-absolute ethanol, and the solution treated with 200 cc. of ether and 300 cc. of hexane. There was recovered propionic acid, I, has been used medically as a 9.5 g. of precipitate, of which a sample decomposed a t cholecystographic agent (Priodax, Selectan). 216-217" (uncor.). The total yield was 29.5 g. (85%). Whereas diiodotyrosine is physiologically active, The ninhydrin test was negative for this material. its N-benzoylated derivative, 11, does not liberAnal. Calcd. for CllH1403XClI2 (497): S , 2.8. Found: ate inorganic iodine metabolically, and the latter 2.8. Diiodo-l-tyrosine Ethyl Ester.-To 7.2 g. of powdered conipound does not have the physiological ester hydrochloride suspended in 60 cc. of wafer was added activity of diiodotyrosine. The requirements of with shaking 30 cc. of 2 N sodium carbonate solution. physiological inertness are also met in I. The solid was filtered and washed copiously with water. After drying in air it weighed 6.2 g. A sample melted 179-180" (uncor.) with decomposition and this melting H O ~ C H , C H C O O H point was unchanged after recrystallization from 50 parts of chlorobenzene. I I XH A n d . Calcd. for CllH1303N12 (461): X, 3.0. Found: I I 3.1 This compound has been obtained previously by iodination of ethyl t y r ~ s i n a t e . ~ N-Benzoyl-l-diiodotyrosine Ethyl Ester.-Ten grams of powdered ester hydrochloride was shaken with 10 cc. of water, 40 cc. of 2 N sodium carbonate solution and 200 I1 cc. of chloroform in a separatory funnel. To this was I added 2.3 cc. of benzoyl ch1oride.h four portions, the mixN-Benzoyldiiodotyrosine has not been syn- ture being shaken vigorously after each addition and until thesized by a satisfactory method, nor has i t been no more carbon dioxide evolved, a t which time there was no more solid phase. The chloroform layer properly characterized. The compound ,may be practically was then filtered and the clear filtrate allowed to evaporate. prepared smoothly by the directions given in the The yield was 10.5 g. (92%); a sample melted a t 153" experimental part. The reactions involved are (uncor.). The solid was recrystallized from 200 cc. of benzene. There was recovered 9.8 g. of m. p. 153" (uncor.). This appeared as dense bundles of very fine needles under the microscope. The presence of the ester grouping in this compound was verified by identification 1 of the ethanol obtained by saponification in diethylene I CeH ,COCl, SalCO, glyc01.~ The distillate after saponification of 2.0 g. of ester yielded approximately 0.2 cc. of ethanol, identified HOCH ?CHS H ~ C O O C ~ H ~ . H --C--~as the 3.5-dinitrobenzoate. u I The compound was not readily soluble in warm sodium bicarbonate solution. +12.9 * 0.3" for 0.797 g. 1 SaOH dissolved in 2 N sodium hydroxide solution to a volume of 1-1 ',CH~CH(NHCOC~H~)COOCIH, 10.0 cc. L I .1nnZ. Calcd. for C18Hl,ON2 (565): 5 , 2.5. Found: 2.1. I N-Benzoyl-diiodotyrosyl Amide.-Four grams of the HO(_)CH~CH(SHCOC~H~) COOH ester was dissolved in 30 cc. of alcohol with warming and I treated with 125 cc. of concentrated ammonium hydroxide. three days the precipitated solid was filtered off. The resultant intermediates are also of experi- After I t weighed 2.0 g. After recrystallization from 18 parts mental pharmacological interest. Another sub- of boiling alcohol samples of various preparations decomstance of interest in this connection is the amide, posed in the range of 234-248" (unc0r.j. Within the limits obtained by the action of ammonia on the ester. of experimental error, 0.5285 g. in 1 K sodium hydroxide solution exhibited no optical activity. A sample of the compound evolved ammonia when heated in boiling 1 S Experimental sodium hydroxide solution. Diiodo-Z-tyrosine Ethyl Ester Hydrochloride.-Thirty d n d . Calcd. for CleHlr03S21? ( 5 3 6 ) : S , 5 . 2 . Found: granis of diiodotyrosine prepared* from Merck I-tyrosine N,5.4. was covered with 500 cc. of absolute ethanol and the mixture saturated with dry hydrogen chloride. The fine N-Benzoyl-Z-diiodotyrosine.-To 9 cc. of 5 -"C sodium needles which separated on chilling weighed 20 g. when dry. hydroxide was added 5.1 g. of the ester and the mixture A sample decomposed a t 217-218" (uncor.) with preheated in a boiling water-bath for thirty minutes. The broTTning. On recrystallization from five parts of 955; I H0./--'\~CH2CHCOOH
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