Ergotamine, total synthesi

The total synthesis of ergotamine (34) opened new possibilities for the preparation of new stereoisomers. Theoretically, almost every isomer now became accessible. 

With the preparation of pure ergotamine, chemical research on ergot also entered a new phase so that, after many decades, it finally became possible to elucidate the structure of the ergot alkaloids and to achieve their total synthesis. This will be shown in the remainder of this chapter. 

Owing to the complete elucidation of the constitution of the compounds obtained by total reduction with LiAlH4 and by thermocleavage, it was possible to propose structural formulas for the peptide alkaloids as early as 1951 (89). These formulas were confirmed by total synthesis of ergotamine after a further 10 years of intensive laboratory research (92). 

Conversion of isomer Lilia with lysergic acid chloride hydrochloride (IVa) in chloroform, with the addition of tributylamine, yielded a compound whose chemical, physical, and pharmacological properties were identical with those of the natural alkaloid ergotamine. Thus, the total synthesis of this alkaloid was accomplished, lysergic acid having already been synthesized at an earlier date (50). 

Scheme 43. Total synthesis of ergotamine by Hofmann and co-workers (209).

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