Crinine alkaloids

Oxidation [1, 391, after citation of ref. 9a], Ferric chloride (1 N) in a 1 1 two-phase system with chloroform oxidizes (1), the trifluoroacetate of methoxy-O-methylnorbelladine, to the dienone (2) in 12% yield. The product (2) on hydrolysis with 2 N Na.CO ,-CHCI l undergoes a second intramolecular condensation to give the ring system of the crinine alkaloids, (3). Jb... 

Key intermediates in the biosynthesis of the crinine alkaloids are norbelladiene and 4 -0-methylnorbelladine (90). It became clear, however, as the result of experiments with doubly labelled precursors that neither these compounds nor 3 -0-methyl-, iV-methyl-, or 3 -OiV-dimethyl-norbelladine were directly involved in mesembrine biosynthesis the moderate levels of incorporation observed were found to be the result of prior fragmentation of the precursors. In an ultimate test... 

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 key intermediate (26) in the synthesis of crinine alkaloids (c/. Vol. 8, p. 138) has now been applied by Tsuda and co-workers to the synthesis of ( )-dihydrolycoricidines (Scheme 6). The reaction of the urethane acid (27) with N-bromosuccinimide gave the bromo-lactone (28), which was converted into the... 

During the course of studies focused on the synthesis of certain crinine alkaloids, we conceived of another and exceptionally concise route to the ABC-ring substructure of galanthamine and hoped that the product would be capable of elaboration in such a way that the nitrogen-containing D-ring of the alkaloid could be annulated to it. The steps associated with the first stage of this study are shown in Scheme 9 and involved a thermally-induced... 

Petit L, Banwell MG, Willis AC (2011) The total synthesis of the crinine alkaloid hamayne via a pd[0]-catalyzed intramolecular alder-ene reaction. Org Lett 13 5800-5803... 

L-phenylanine alkaloids alkaloids Crinine Eloramultine Galanthamine Galanthine Haemanthamine Lycorine Lycorenine Maritidine Oxomaritidine Vittatine... 

From L-tyrosine, or alternatively from L-phenylalanine, there is one further alkaloid biosynthesis pathway. This is the galanthamine pathway (Figure 38). Galanthamine synthesizes with tyramine, norbelladine, lycorine, crinine, N-demethylnarwedine and Al-demethylgalanthamine. Schiff base and reduction reaction, oxidative coupling and enzyme NADPH and SAM activity occur in this pathway. Schiff base is a reaction for the ehmination of water in formation with the C—N bonds process. 

Pyrrolophenanthridines and Related Alkaloids Lycorine and Related Alkaloids Galanthamine and Related Alkaloids Crinine and Related Alkaloids Tazettine and Related Alkaloids... 

The alkaloids of the crinine group have been the objects of intensive synthetic investigations, and a number of general and useful strategies have been developed. The biogenetic approach to crinine (359) and maritidine (387) has been explored (176,191-196), and an attempt to access pretazettine (395) via an... 

The alkaloids related to crinine (359), which possess the 5,10b-ethanophen-anthridine nucleus, have been the subject of extensive synthetic investigations (190). Alkaloids of this family bearing oxygen functionality at C-ll occupy a special position since they are possible biosynthetic and chemical precursors of the subgroups that incorporate a 2-benzopyrano[3,4-c]indole ring such as those alkaloids related to pretazettine (395), tazettine (397), and macronine (401) and the methanomorphanthridines such as montanine (584). 

Thus, although the yields in the oxidative cyclizations of diphenolic substances and their derivatives may sometimes be lower than might be desired, this biomimetic approach constitutes a rapid and concise entry to the crinine family of alkaloids. Continued research in this area should lead to the development of improved synthetic methodology and tactics for effecting this important conversion, resulting thereby in highly useful syntheses of members of this class of naturally occurring bases. 

Another concise strategy for the synthesis of alkaloids related to crinine features the application of a general and useful procedure for the elaboration at a carbonyl center of a quaternary carbon atom bearing differentially functionalized alkyl substituents. The application of this methodology to the total syntheses of ( )-crinine (359) and ( )-buphanisine (361) (Scheme 46) commenced with the... 

Doepke and co-workers have isolated more new alkaloids from Hymenocallis arenicola. Havanine (1) is a new member of the crinine group the presence of two methoxyl groups and one attached to an sp3 carbon was indicated by the n.m.r. spectrum, and the structure of the alkaloid was proposed mainly on the basis of the mass spectrum.2 Structure (2) for caribine was assigned as a... 

The availability of the enantiomeric alkaloids vittatine (284) and crinine in labeled form through separate feeding experiments with labeled 343 in Pancratium maritimum L. and Nerine bowdenii, respectively, provided experiments which indicated the absolute configuration of narciclasine. Thus, the two alkaloids were obtained from [3, 5 -3H2]-O-methylnorbelladine. Experiments with multiply labeled 343 have previously shown that no 3H loss takes place during the biosynthesis,... 

Nevertheless, such rearrangements offer a concise route to some alkaloids. For example, the total synthesis of crinine was achieved with the silver-promoted formation of hydroindolone as the key step (Scheme 3.40).59... 

The use of enamide photocyclization in the synthesis of Amaryllidaceae alkaloids has remained a basic study and so far limited only to the synthesis of the skeletons of lycorine and crinine, as well as intermediates in the total synthesis of haemanthidine and nortazettine, and some of the degradation products of these alkaloids. 

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