Relationships between ergotamine and ergotaminine

All doubts as to the correctness of the structure of lysergic acid were removed by a synthesis first of all of rac-6,8-dimethylergoline and then rac-dihydrolysergic acid but the comparisons were made difficult because of the production of isomers (three asymmetric centres are involved). The early approaches to the synthesis of lysergic acid itself were frustrated by its tendency under acidic conditions to isomerize irreversibly into the isomeric naphthalene . A synthesis was finally accomplished in a simple elegant manner in which the key concept was the introduction of the indolic double bond as the last step (Chart 4.7). 

Jacobs, W. A. and Craig, L. C., The ergot alkaloids XI. Isomeric dihydrolysergic acids and the structure of lysergic acid, J. Biol. Chem., 115, 227 (1936). 

As shown in Chart 5.1, a wide variety of alkaloid skeleta are derivable from Type I precursor and tryptamine by further ring closures. It is worth pointing out that in so far as they have been investigated, they all have had the same stereochemistry for the carbon equivalent to C-15 of yohimbine. In this chapter, certain tetrahydro-j8-carboline alkaloids, viz., the yohimbines, their ring E seco equivalents and ring E oxygen heterocycles will be discussed since they show much chemistry in common. Over the years most of their degradation products have been synthesized, they have been interrelated, their absolute stereochemistries derived, and some have been synthesized. For these reasons they have become valuable reference compounds. 

Three aspects of their chemistry are important 1. The stereochemistry at C-3 its determination and control. 2. The chemistry of ring E (of the substituents in the case of the seco alkaloids). 3. The determination of the configuration and conformation of the ring systems. The solution to these problems was greatly accelerated in the years following 1952 because of the discovery and commercial importance of the antihypertensive drug, reserpine, a derivative of 3-epialloyohimbane (see Chart 5.3). 

The Yohimbanes. The yohimbines (Table 5.1) take their names from their first isolated and most ubiquitous member, yohimbine. They are found in rubiaceous and apocynaceous plants. Now that their structures have been established, they could be named systematically as derivatives of the pentacyclic diazahydro-carbon, 

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