Natural clavicipitic acid

Clavicipitic acid (129) (naturally occurring as a mixture of C-10 epimers) has been identified as a metabolite which is at a shunt from the main line of... 

The revised structure for clavicipitic acid, suggested earlier by King etal.,44a has been confirmed, and the stereochemistry elucidated, by X-ray crystal-structure analysis.446 The major component of the naturally occurring mixture that constitutes clavicipitic acid was obtained pure by t.l.c. on silica gel, and proves to have the (55,10/ ) stereochemistry depicted in (53). The minor component of the mixture is presumably the (55,105)-diastereoisomer. It should be noted that, at present, the absolute configuration of clavicipitic acid rests only on its biogenetic derivation from L-tryptophan.446... 

The Heck reaction has been widely used for the synthesis of many natural and unnatural products. The Heck reaction catalyzed by palladium acetate in water using a water-soluble ligand has been employed for the synthesis of clavicipitic acid (Scheme 5.24). 

Clavicipitic acid (1) is an unusual ergot alkaloid biosynthesis derailment product and occurs in nature as a mixture of cis- and ran -diasteromers (la/lb). The synthesis of the N-acetyl)methylesters of la and lb has been achieved by the following route starting with 2-bromo-6-nitrotoluene (X) ... 

For the production of natural products on an industrial scale, fermentation processes are often preferable in comparison to chemical processes. In biosynthesis processes, natural products may be generated efficiently and cleanly via enzymatic catalysis 185). Thus, the development of synthesis approaches similar to their biosynthesis is one of the main objectives of the synthesis community. To pursue this goal, Yokoyama and co-workers developed a bio-similar three-step synthesis of optically active clavicipitic acid (175) 186), which was isolated from natural sources as an isomeric mixture (Scheme 4.10) 187). 

Clavicipitic acid and its plausible decarboxylation product aurantioclavine were detected as metabolites P. aurantiovirens (Kozlovsky et al., 1981). Later, N-6-ethylaurantioclavine has been isolated and it s structure was elucidated (Kozlovsky et al., 1997a). It is the first case of natural ergot alkaloid containing N-6-ethyl group (Figure 2). 

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