PROCESS FOR THE PREPARATION OF ERGOT. AMINE, ERGOTAMANIENE AND ERGOMETRin E BY SAPROPHYTEC CUSTURE OF ERGOT (CLAVE. CEPS PURPUREA FR TUL.) AN WATRO AND SO LATION OF THE ASEKALORDS THUS PRODUCED

1. Claim. (C. 195-81) The present invention relates to a process for the prepa ration of ergotamine, ergotaminine and ergometrine by Saprophytic culture of ergot (Claviceps purpurea Frl Tul.) in vitro and isolation of the alkaloids thus pro duced. According to this invention, a suitable strain of ergot (Ciaviceps purpurea Fr Tul.) can be cultured in vitro on a suitable nutrient medium under certain prescribed conditions in such a way that it produces ergotamine, ergotaininine and ergometrine in quantities large enough for isolation in a pure crystalline form on a preparative scale. This invention is of fundamental importance be cause it is capable of rendering the production of me dicinally important ergot alkaloids independent of natural occurrence and of the artificial culture of ergot in the fied. The saprophytic culture of ergot has been reported several times in the literature and it has been claimed that ergot alkaloids have been detected both in the my celiusa and in the culture medium. This claim rests on the results of color tests, principally upon the reaction to the test of van Urk with p-dimethylaminobenzaldehyde (van Urk, Pharm. Weekbl. 66, 437 (1929]). However, this reaction is not specific, since indole and many indole derivatives also give a reddish-violet coloration with this reagent (Ehrlich, Pharm. Zentralh., 1918, 114) and may be mistaken for ergot alkaloids. It is known that various micro-organisms are capable of producing indole or in doie derivatives in nutrient medium. For this reason, a positive van Urk reaction cannot be taken as definite evidence of the presence of ergot alkaloids in total ex tracts. in many cases, however, the saprophytic cultures of ergot described in the literature were tested for the pres ence of ergot alkaloids not only by means of color re actions, but also by biological methods (e. g. uterotonic activity). Nevertheless, when applied to complex ma terial Such as culture filtrates or extracts of mycelium, these methods of examination cannot be regarded as specific either, since other substances, e. g. histamine, also exert a more or less marked uterotonic action. That the methods of culturing ergot in vitro described in the literature have not so far led to the successful production of ergot alkaloids on a preparative scale is convincingly demonstrated by the fact that the ergot employed for the manufacture of the active principles is still obtained exclusively by artificial culture in the field or gathered from places where it occurs wild. Nevertheless, brief mention may be made of the var ious attenpts of this nature which have been described in the literature. McCrea (Amer. J. Bot. 18, 50 (1931; U. S. Patent No. 2,056,360) claimed that he had suc ceeded for the first time in producing ergotoxine, hist Patent Office