Lycorine alkaloids

The lycorine alkaloids come from plants such as daffodils. Among the simplest are the lyco-ranes 71-73 differing only in stereochemistry. They contain a saturated six-membered carbocyclic ring and that might make you think immediately of the Diels-Alder reaction. 

The group of activated olefins, which has so far probably received most attention in radical cyclizations, are enamides. Syntheses of various natural products, especially alkaloids, have been successfully completed using this strategy. Cyclizations onto enamides of the 6-endo type led to erysotrine [76] and lycorine alkaloids [77-79]. The skeleton of hydroapoerysopines [80] was successfully constructed by a 1-endo cyclization. Two new examples of radical tandem reactions, which commence with a 1-endo type cyclization, have appeared in recent literature. Construction of the cephalotaxine core structure 29 was achieved from enamide 30 in only one step (Scheme 11) [81]. 

This method can be applied to the total synthesis of natural products. The lycorine alkaloids anhydrolycorinone and hippadine have a pyrrolo[3,2,l-de]phenanthridine framework and have been isolated from Amaryllidaceae plants [26]. Hippadine exhibits reversible inhibition of fertility in male rats. Diverse synthetic approaches to the pyrrolophenanthridine alkaloids have been developed because of their potent biological activities [27[. We applied the iron(O)-mediated arylamine cydization described above to a concise synthesis of anhydrolycorinone and hippadine (Scheme 15.7) [28]. 

Although one-electron oxidation of arenes by thallium trifluoroacetate presumably does not proceed via formation of a discrete aiylthallium bond, some examples involving oxidative cyclization mediated by thallium trifluoroacetate will be considered here. Schwartz and Hudec employed thallium trifluoroacetate to effect an intramolecular cyclization of the amide (41) to give a key intermediate (42) in their projected synthesis of lycorine alkaloids (Scheme 16). Interestingly, when the bromine was replaced by a hyctogen the yield was poorer. 

A photochemical ring construction similar to that described in Scheme 5 was used in the synthesis of the aromatic lycorine alkaloid ungeremine (51) (Scheme 6). Photocyclization of the somewhat inaccessible imine (48) gave the phenanthridine derivative (49) in 21 % yield which upon metal hydride reduction and cyclization with phosphorus tribromide afforded the quaternary salt (50) which was shown to be identical with the methyl ether of ungeremine (51) obtained as shown. 

The intramolecular Diels-Alder reaction of 2-pyrones with alkynes has recently been exploited in synthesizing [a]-annelated carbazoles 11, [c]-annelated carbazoles 12, and lycorine alkaloids 13. ... 

Fortucine 112, first isolated from the Fortune variety of narcissus by Tokhtabaeva et al. [43] in 1987, is a Lycorine alkaloid. To clarify the structure, Zard and coworkers [44] carried out the first total synthesis of ( )-fortucine using a radical domino process as the key step (Scheme 5.23). It was suggested that an amidyl-nitrogen radical is generated from 110, followed by a 5-exo-trig cyclization in sequence with... 

Furthermore, the same group illustrated that this protocol could be successfully applied for the construction of the key indole core of lycorine alkaloid Hippadine 118 (Scheme 9.45) [201]. Later, it was also shown that this transformation could be... 

Other target molecules have been synthesized by this general approach. The skeleton of the lycorine alkaloids has been constructed by Stork and Morgans, " as shown, from the triene (44). Examples of the imino-variation of the... 

Amide Formation. The synthesis of an amide can be accomplished by initial reaction of an acid with PhsP-CCU and then reaction of the intermediate with 2 equiv of the appropriate amine. A tertiary amine, such as Diisopropylethylamine, can be employed as the HCl scavenger in cases where one would not want to waste any of a potentially valuable amine.This method has been used in the construction of an amide in the synthesis of the skeleton of the lycorine alkaloids (eq 29). ... 

---