Ergot alkaloids lysergic acid synthesis

An unsuccessful attempt was made to apply this methodology to a total synthesis of the Ergot alkaloid lysergic acid (Scheme 19) [42]. Therefore, aldehyde olefin 107 was prepared and was exposed to the Kresze conditions with the... 

Uhle, EC. and Jacobs, W.A. (1945) The ergot alkaloids. XX. The synthesis of dihydro-J/-lysergic acid. A new synthesis of 3-substituted quinolines. J. Org. Chem., 10, 76-86. 

Protoplasts of C. purpurea have been prepared which are able to synthesize the peptidic ergot alkaloids ergotamine (69) and ergocryptine de novo.63 Various radioactive amino-acids were incorporated into the alkaloids, and D-lysergic acid (70) stimulated their utilization. It was the only precursor to stimulate the synthesis of alkaloids, and the proposal was made that the concentration of (70) in the cells is a rate-limiting factor in alkaloid synthesis. 

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. 

So far, reductive photocyclization has been successfully applied to the synthesis of yohimbine-type compounds (54), benzo[/]quinolines, and ergot alkaloids including lysergic acid (55-57) (Scheme 19). 

Figure 1 Key intermediate and enzymes from the first committed step in ergot alkaloid biosynthesis through the synthesis of lysergic acid. Simple amides of lysergic acid and ergopeptines are covered in Figs 2 and 3, respectively. Abbreviations DMAPP = dimethylallyl pyrophosphate DMAT = dimethylallyl tryptophan AdoMet = S-adenosyl-methionine.

Since the first chemical experiments of Hofmann with ergot alkaloids in the 1930s and the first total synthesis of lysergic acid (133) by Kornfeld and Woodward in 1956 137), ergot alkaloids have attracted interest from the chemical synthesis community. In this chapter, synthetic approaches within the last two decades are presented, wherein attention is focused on syntheses using the application of modem catalytic methods and metal-organic reagents. Within the body of... 

Jacobs, W.A. and Craig, L.C. (1937) The ergot alkaloids. XII. Synthesis of substances related to lysergic acid./. Biol. Chem., 120,141-150. 

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