Amaryllidaceae alkaloids synthetic studies

Synthetic studies on the Amaryllidaceae alkaloids have continued at a high level of activity. Details concerning the stereospecific total synthesis of haemanthidine (11)... 

Synthetic Studies on Amaryllidaceae and Other Terrestrially Derived Alkaloids... 

The crinine alkaloids, which can embody either enantiomeric form of the 2,3, 4,4a-tetrahydro-l//-6//-5,10b-ethanophenanthridine framework, represent an important sub-class within the Amaryllidaceae alkaloid family [53]. Many members of this subclass display interesting biological properties including immuno-stimulatory, cytotoxic and anti-malarial activities. As a consequence, they have been the subject of numerous synthetic studies [53]. 

The alkaloid galanthamine (169) has been obtained from various Amaryllidaceae species including daffodils, the red spider lily Lycoris radiata) and the Caucasian snowdrop (Galanthus woronowii). Its effectiveness as a centrally acting, selective, reversible and competitive inhibitor of acetylcholinesterase has resulted in galanthamine being introduced into the clinic in both the USA and Europe for the symptomatic treatment of mild to moderate forms of Alzheimer s disease [57]. These and various other intriguing feamres of this alkaloid have prompted extensive synthetic studies of it [57]. 

In our study, we have realised a highly enantioselective alleviation of 2-aiylcyclohexanones by installing an achiral auxiliary, iV,Af-diphenylamino-methylene group at the 6-position of cyclohexanones (Scheme 17.25). The auxiliary was readily removed from the alkylation product by simple basic hydrolysis. Further synthetic utility of this asymmetric alleviation was successfully demonstrated in a short total synthesis of an amaryllidaceae alkaloid, (-l-)-crinane. 

Lycorine is the most abundant alkaloid in plants of the Amaryllidaceae. Several syntheses of racemic lycorine had been reported prior to our initiation of studies directed at an asymmetric synthesis of the unnatural enantiomer 64. 2 a common theme in all of the syntheses of ( )-lycorine has been the utilization of either an intermolecular or intramolecular Diels-Alder construction of the key C-ring of the alkaloid. This six-membered ring presents a rather formidable synthetic challenge because of the four contiguous stereogenic centers, the trans 1,2-diol moiety, and the juxtaposition of the aromatic substituent and the carbon-carbon double bond. 

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