The synthesis of histidine / by Frank Lee Pyman.

  • Pyman, Frank Lee.
Date:
[between 1900 and 1909?]
Catalogue details

Licence: In copyright

Credit: The synthesis of histidine / by Frank Lee Pyman. Source: Wellcome Collection.

    2/28 (page 1387)
    (H) was formed in a yield amounting to 49 per cent, of the theoretical: NH-CH CH=N >C-CH2C1,HC1 + 20HNa(C02Et)2 = (I.) NH-CH CH=N >C-CH2-CH(C02Et)2 + CH2(C02Et)2 + 2NaCl (II.) This ester, on hydrolysis with barium hydroxide, gave the corre¬ sponding acid, 4:{pTb)-glyoxalinemethylmolonic acid (III), together with a certain amount of /3-glyoxaline-4(or 5)-propionic acid (IV), produced from the former by the removal of carbon dioxide. 4(or 5)-Glyoxalinemethylmalonic acid is a beautifully crystalline compound, which, on heating, loses carbon dioxide at 180°, and is converted into )8-glyoxaline-4(or 5)-propionie acid (IV), a substance which has previously been prepared by Knoop and Windaus (Beitr. chem. Physiol. Path., 1905, 7, 144), both by the degradation of histidine, and synthetically from glyoxylpropionic acid: CH-NH 11 C-N >CH CH2-CH(C02H)2 (III.) —> CH-NH ^ 11 >CH c— ch2-ch9-co2h (I VO Similar condensation products were obtained by the action of 4(or 5)-chloromethylglyoxaline hydrochloride on ethyl sodioaceto- acetate and ethyl sodiomethylacetoacetate, ethyl 4(or 5)-glyoxaline- methylacetoacetate (V) and ethyl 4(or b)-glyoxalinernethylmethyl- acetoacetate (VI) being formed: CH-NH 11 C-N >CH 0H2*CH(C0Me)*C02Et (V) CH-NH I ! C—-N >CH CH2-CMe(C0Me)-C02Et (VI.) In view of these results, it seemed of interest to attempt the condensation of this salt with ethyl sodiochloromalonate, since this might lead to a synthesis of histidine, for Conrad (.Annalen, 1881, 209, 241) has shown that this ester condenses with benzyl chloride, forming ethyl benzylchloromalonate, although it does not condense with less reactive alkyl chlorides. On experiment, it was found that 4(or 5)-chloromethylglyoxaline hydrochloride readily condenses with ethyl sodiochloromalonate,