Alkaloids diene double bonds

The total syntheses of these pepper alkaloids are not those of pyrrolidines but rather syntheses of their acid parts. Thus dihydrowisanidine (137) has been prepared by a series of reactions, the key step of which is the formation of the carbon-carbon double bond by a Wittig-Homer reaction (217, 218). Schemes 41 and 42 summarize two syntheses of okolasine from sesamolmethyl ether (279) of course, routes to okolasine also yield the corresponding piperidine alkaloid wisanine. Molybdenum-catalyzed elimination of allylic acetate (149) yielded (E,E)-diene ester 150 en route to trichonine (220) worthy of note is the use of an aluminum amide in the preparation of amide 143 from ester 150 (Scheme 43). 

Vogel and Delavier (26) reported a synthesis of the 6-azabicyclo[3.2.2]nonane skeleton 130 using an intramolecular azide-alkene cycloaddition strategy (Scheme 9.26). When refluxed in xylene, the azide 126 underwent an intramolecular 1,3-dipolar cycloaddition with the internal alkene. Nitrogen extrusion and subsequent rearrangement led to a mixmre of compounds 128, 129, and 130. Reactions of azides with the double bond of dienes were also used in various total syntheses of alkaloids, and will be discussed later in Section 9.2.2. 

A synthetic approach to the class of tq)oriAine alkaloids centers on [4 + 2] cycloadditions of benzynes to the cisoid 1,3-diene (531), which contains one double bond as part of a benzene ring (Scheme 125). 2 ... 

The presence of two hydroxyls (one of them allylic), one dimethyl-amino group, and two secondary tertiary double bonds in the pregnane skeleton of this alkaloid was established from IR- and XMR-spectra. Comparison of the NMR-spectrum with those of the stereoisomeric 3,16-dihydroxypregna-5,17(20)-dienes reported in the literature 60) showed that the signal of the 18-methyl occupied the position (9.24 t) which was in agreement with the a orientation of the 16 hydroxyl and trans configuration of the olefinic side chain as expressed in the formula LXVIII 59). 

Dendrobium Alkaloids.—8-Epidendrobine (14) has been synthesized employing a route involving a diene isomerization in a Diels-Alder reaction (Scheme 3). To account for the unexpected stereochemical result of the latter addition [(12)->(13) and epimeride] it is proposed that ester (15) assumes a very hindered conformation in the transition state, involving no secondary orbital overlap between diene and ester groups. However isomerization of the trisubstituted double bond to give (16) leads... 

In 1952 Edwards and Marion (62) observed the apparent diene chromophore in the pyro compounds derived from the aconitine-type alkaloids with no hydroxyl group at the C-15 position. Wiesner and coworkers (63) reported an unexpected UV absorption (Amax 245 nm, emax 6300) for pyrodelphonine (32) and pyroneoline (33), which disappears upon acidification. To explain the unusual behavior of these pyro compounds, they postulated the participation of the lone-pair electrons of the nitrogen with the C-7-C-17 cr bond and the ir system of C-8-C-15 double bond in an excited state resembling structure 32A in pyrodelphonine and 33A in pyroneoline. Later, the same phenomenon, was also explained using valence bond language by Cookson and his co-workers... 

Finally, the typical position and the number of olefinic bonds in the A and B ring have led to a further subdivision into dienoids and alkenoids in both alkaloid series. The former are characterized by a conjugated diene unit covering C atoms 1, 2, 6, and 7, while the latter possess only one double bond in the 1,6-position (see Fig. 2). 

Amino complexes of rare-earth elements can undergo intramolecular alkene insertion rather than alkene activation followed by nucleophilic attack (Scheme 6.59). Treatment of the amino diene 6.170 with a scandium complex 6.174 resulted in insertion of one double bond to give a d5-pyrrolidine 6.171. Raising the reaction temperature then caused insertion of the second alkene to give the pyrrolizidine 6.172. The thiophene group had been chosen to activate the first alkene it also serves as a surrogate alkyl group, and the synthesis was completed by desulfurization-reduction. The product is the alkaloid, xenovenine 6.173 (see Schemes 6.65 and 6.74 for related syntheses, and Scheme 9.46 for a different approach.)... 

The intramolecular aza Diels-Alder cycloaddition is also a valuable tool for the synthesis of alkaloids as demonstrated by the stereocontrolled synthesis of ( )-lepadifor-mine 137 (Scheme 41.29). This tricyclic alkaloid has been isolated from several species of Clavenia and Polycitoridae sea squirts and is moderately cytotoxic toward various tumor cell lines and effective to block potassium ion channels. Initial attempts to perform the aza Diels-Alder reaction with the racemic imino-diene t-butyl ester 134 in toluene at temperatures up to 165°C did not lead to the observation of any cycloadducts but to double bonds isomerization products. The corresponding free carboxylic acid only suffered decarboxylation. The addition of trifluoroacetic acid to generate an imminium species was also unsuccessful. 

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