Amaryllidaceae alkaloids galantamine

Galantamine and other amaryllidaceae alkaloids (refer to Structures 8)... 

Galanthamine (= Galantamine Lycoremine Reminyl) (galanthaman Amaryllidaceae alkaloid) clinically used for Alzheimer s disease (acetylcholine signalling-linked dementia)... 

Lastly, norbelladine (top of Scheme 1.7) is issued from the reductive amination of 3,4-dihydroxybenzaldehyde (derived from phenylalanine) with tyramine (derived from tyrosine) and constitutes a biosynthetic node leading to Amaryllidaceae alkaloids such as galantamine, crinine, or lycorine depending on the topology of phenolic couplings. In all these biosynthetic routes, radical phenolic couplings are key reactions for C—C and C—O bond formations and rearrangements [30, 31]. 

Several members of the Amaryllidaceae family of alkaloids display pronounced biological activities, and some Amaryllidaceae plants have played an important role in traditional herbal medicine for the treatment of various ailments. The most prominent examples of Amaryllidaceae alkaloids of biological relevance are narciclasine (55) and its congeners (pancratistatin and 7-deoxypancratistatin) and galantamine (62) (also commonly spelled galanthamine). These natural products also find application in modem medicine, and in this respect, pancratistatin is used in clinical... 

Chemical routes to narciclasine and 7-deoxypancra-tistatin (narciclasine type) as well as galantamine are described in the synthetic section of this chapter. The biosyntheses of these two types of Amaryllidaceae alkaloids are described in the following, while the discussion of other interesting classes of Amaryllidaceae constituents is omitted. 

Reduction of the carbonyl moiety in narwedine (304) with lithium aluminum hydride completed the synthesis of galantamine. The Amaryllidaceae alkaloid was obtained in quantitative yield as 6 4 mixture with its epimer. 

Kita anployed a hypervalent iodine species for the oxidative cyclization of phenol 310 as shown in Equation 12.54-1, Scheme 12.54 [190]. When allowed to react with phenyliodinedll) bisftrifluoroacetate) (FIFA), 310 delivered the desired galantamine skeleton in 40% yield. The cyclization most likely proceeds via the initial reaction of the phenolic oxygen with the hypervalent iodine reagent and subsequent nucleophilic attack of the second electron-rich aromatic ring onto the intermediary formed cation radical intermediate. Kita and coworkers outlined the importance of the fluorinated solvent. When carried out in benzene or dichloromethane, the desired product was not formed. A similar oxidative coupling protocol has been successfully employed by the authors for other Amaryllidaceae alkaloids [191]. 

Several other protocols have been reported. For further information, review articles on Amaryllidaceae alkaloids and galantamine should be consulted [48],... 

Galantamine (7, Razadyne , Reminyl , Nivalin ) is a recently approved drug for the treatment of early-onset Alzheimer s disease [12]. Galantamine (or galanthamine) is an Amaryllidaceae-type alkaloid first purified from the snowdrop (Galanthus woronowii) in... 

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