Ergoline system

Asymmetric cyclization to tricyclic ergolines. The ergoline system of ergot alkaloids can be obtained in fairly high enantioselectivity by cyclization of 2 catalyzed by Pd(0) complexed with a chiral ligand and a base. The ligands BINAP,... 

Chanoclavine (LXXV) (108) is the only known ergot alkaloid in which the D ring of the ergoline system is open. LXXV easily forms an 0,N-... 

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. 

Because of the ergoline system is only slightly puckered, the steroid chemistry nomenclature using designation a- for a substituent below and for that above the plane is convenient and is therefore used very often for semisynthetic derivatives e.g., lOa-methoxydihydrolysergol. 

The possible intramolecular acylation of 3-(3-indolyl)propionic acids as a primary step in a route to the ergoline ring system of the ergot alkaloids has received wide attention (80T3123, 81H(16)267). When the 2-position of the indolylpropionic acid is unsubstituted, intramolecular cyclization to that position occurs (57JCS497). The reaction probably involves... 

A nitroalkane has also served as nucleophile in the cyclizadon as shown in Scheme 8E.32 to give the ergoline ring system in high diastereo- and enantioselecdvity. The initially obtained modest enanitoselectivity (66% ee) by using a catalyst derived from Pd2(dba)3 CHCl3 and (5, 5 )-chiraphos (2) was optimized to 95% ee by using a complex of (S)-BINAP (ent-4) and Pd(OAc)2 [169,170], The obtained tricyclic alkylation product provided an expeditious access to (-)-chanoclavine I. 

Ergot alkaloids are mycotoxins produced (mainly) by Claviceps species which have deleterious effects on the central nervous system of mammalia on the other hand, they have a long biotechnological tradition with manifold applications in therapy of human central nervous system (CNS) disorders (for reviews, see Keller and Tudzynski, 2001 Tudzynski et al., 2001). Chemically they are 3,4-substituted indole derivatives having a tetracyclic ergoline ring structure (Fig. 2). 

Figure 2 Ergot alkaloids schematic structure of the ergoline ring system, of D-lysergic acid amides, and of agroclavine as an example for the "simple" clavine alkaloids. (Modified from Tudzynski et al., 2001.)...

Most of the natural ergot alkaloids possess the tetracyclic ergoline ring system as their characteristic structural feature (Fig. 1). 

The tricyclic system has also been constructed from an indole via electrophilic substitution reactions at positions 3 and/or 4. Synthesis of tricyclic ergoline synthons from 5-methoxy-lH-indole-4-carboxaldehyde has been described [45]. Sodium cyanoborohydride mediated reductive amination provided easy access to l,3,4,5-tetrahydrobenz[cd]indole-4-amines, compounds which show specificity for serotonin and dopamine receptors. 

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