25,37 synthesis Ergometrine

As the resolution of the racemic lysergic acid into its optical antipodes and the synthesis of ergometrine had been described earlier by Stoll and Hofmann (25, 66), this meant that not only had the synthesis of d-lysergic acid been achieved but also the first total synthesis of an ergot alkaloid. 

In the last few years, further processes for the partial synthesis of ergometrine and other lysergic acid derivatives of the amide type have been discovered. 

Partial synthesis of a great number of ergometrine analogs, in which the amino-propanol moiety is replaced by other amino alcohols or by simple primary and secondary amines, results in significant shifts in the pharmacodynamic profile these shifts are especially evident quantitatively, but also qualitatively. 

Fig. 1. a-Mannosidase-catalyzed synthesis of elymodavine a-mannoside (- -), ergometrine a-mannoside (-A-) and chanodavine a-mannoside (- -). The initial concentration of mannose and respective alkaloid were 3 and 0.2 M, respectively. The enzyme concentration was 10 U/ml [21]... 

Figure 31 Possible pathway of ergometrine synthesis on a d-Iysergyl peptide synthetase involving post-assembly modifications by in situ reduction of covalently bound d-Iysergyl-alanine to d-Iysergyl-alanine-aldehyde with subsequent reduction to ergometrine...

---