Ergoline precursors

Metabolites of the ergoline type [as (128)], as well as those of type (119), have been isolated from Penicillium roqueforti. The incorporation has been observed of radioactive samples of tryptophan and mevalonate into both series of metabolites, and of histidine into those of type (119).44 Diversion from tryptophan into the two independent biosynthetic pathways is initiated on the one hand by the formation of (122) and on the other by reaction with histidine to give a diketopiperazine precursor for metabolites such as (119). Which route is followed is temperature-dependent. 

Ergot Alkaloids.—The tryptophan and tryptamine derivatives (30) and (31) respectively, labelled in each case with 14C at the carbinol carbon, have been shown20 to be precursors of the alkaloids agroclavine (32) and elymoclavine (33). These results throw further light on the sequence of intermediates leading from tryptophan to the ergoline system. 

In the course of their studies on the biosynthesis of ergot alkaloids. Robbers and Floss isolated clavidpitic acid, a new indolic amino acid [89]. Based on the X-ray crystal data of the major isomer and the assumption that the stereocenter at C-5 retains its stereochemistry from L-tryptophan, the structure shown in Scheme 59 was assigned [90]. By performing feeding experiments on Claviceps sp. SD 58 with clavicipitic acid (biosynthetically labeled), the laboratories of Floss [90] and Anderson [91] independently determined that clavicipitic acid is not a precursor to elymoclavine. Instead, Floss argues that it arises from ... a derailment of the metabolism leading to the tetracyclic ergolines between the first and second pathway-specific steps, the isoprenylation of tryptophan and the N-methylation of 4-(y,y-dimethylallyl)-tryptophan (DMAT). Anderson and co-workers isolated an enzyme, DMAT oxidase, from Claviceps sp. which catalyzes the formation of clavicipitic acid from DMAT [92]. The enzyme, which requires... 

Nitroacetic acid esters and anudes are potential precursors of amino acids. They are good substrates in Pd(0)-catalyzed allylation with carbonates (Scheme 18) the same as the structurally related open-chain and cyclic a-nitroketones. An intramolecular version is aimed at the preparation of precursors of alkaloid ergoline. 3,4-Dimethylenecyclopentane nitroacetate is prepared in one synthetic step from allyl carbonate (R = Br, R = H) including a C—C bond formation by Pd-catalyzed reductive coupling.f There are more examples of Pd(0)-catalyzed allylation of nitroderiva-tives including nitromethane.f ... 

Fig. 23.1 L-tryptophan as precursor for ergoline ring formation as a common scaffold of EAs...

BIOSYNTHESIS OF THE ERGOLINE RING 5.3.1. Precursors of the Ergoline Ring... 

Figure 4 Biogenetic precursors of the ergoline ring system...

The utility of this cocyclization was shown in the synthesis of the ergoline framework when an ethynylic indole was employed, as in Scheme 5. The requisite 4-ethynyl-3-indoleacet(Miitrile (24) was prepared readily from the 4-bromoindole precursor followed by palladinm-catalyzed trimeihylsilyl-ethynylation-deprotonalion. 

Elymoclavine (1.4% inc. This incorporation is not considered significant, since genuine precursors of the ergoline ring system usually give incorporations of 20-60%),... 

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