Lycorane Amaryllidaceae alkaloids

Likewise, the P-azidation reaction has been applied to the enantioselective synthesis of the core structure of lycorane Amaryllidaceae alkaloids. The key intermediate 478 in this synthesis was obtained by p-azidation of the TIPS derivative 477 as a mixture of trans- and CM-diastereomers (3.5 1 ratio) (Scheme 3.189) [566]. 

Magnus developed also a combination of iodosyl benzene and trimethylsilyl azide to azidate the j8-carbon of silyl enol ethers (Scheme 8.22). ° ° The total synthesis of lycorane amaryllidaceae alkaloids takes advantage of this process. A tentative ionic mechanism is proposed for this process. However, involvement of radicals cannot be totally excluded. Under the same reaction conditions, anilines and amides lead to the isolation of C-H substituted products at carbon atoms adjacent to nitrogen (Scheme 8.23). These azidoamines/azidoamides are precursor of iminium/acycliminium ions that are useful intermediates for C-C bond formation. 

One of these products (49) was used as a key intermediate for the synthesis of the Amaryllidaceae alkaloids a- and /-lycorane (Scheme 12)53. A copper-catalyzed Grignard reaction with 49 afforded 50 via a selective y-anti displacement of the chloride. Hydrogenation followed by Bischler-Napieralski cyclization gave 51. Interestingly, reversal of the latter two steps gave the isomer 52 where an epimerization at the benzylic carbon had occurred in the cyclization step (>99% selectivity). Subsequent reduction of the amide in each case afforded the target molecules a- and y-lycorane, respectively. The purity of the final product was very high with respect to the opposite stereoisomer. Thus <0.2% of /-lycorane was present in a-lycorane and vice versa. 

Lycorine. Boeckman s particularly elegant synthesis [65] (Scheme 41) of the most abundant Amaryllidaceae alkaloid, (-)-lycorine (245) [66], known since 1877 [67], involved an intramolecular Diels-Alder reaction of an appropriately functionalised azatrienic system. This approach (A + D - AD - ADCB) somewhat reminiscent of the one used by Stork for ( )-7-oxo-a-lycorane [68], possessed the virtue of establishing the correct stereochemistry of four... 

Tlie intramolecular 1,4-chloroamination of 89 was applied to the synthesis of the amaryllidaceae alkaloids a- and y-lycorane (Scheme 8-34) [114]. The hexahydroindole 90... 

Synthetic Applications The intramolecular 1,4-chloroamination of 108 was apphed to the synthesis of amaryllidaceae alkaloids a- and ylycotane (Scheme 11.40) [129]. The hexahydroindole 109 obtained was transformed to the target alkaloid a-lycorane by a copper-catalyzed reaction with 3,4-(methylene-dioxy)phenyhnagnesium bromide, followed by hydrogenation, the Bischler-Napieralski cyclization, and LiAlH reduction. When the Bischler-Napieralski cyclization was carried out before the hydrogenation, ylycorane was the sole product. 

Lycoranes belong to the family of Amaryllidaceae alkaloids, structures defined as a goldmine of potential new drugs. Their derivatives and congeners exhibit antiviral activity, cholinesterase inhibition and promising results in the treatment of Alzheimer s disease. 

An interesting approach to the enantioselective synthesis of the Amaryllidaceae alkaloid (- -)-7-lycorane by employing a palladium-catalyzed asymmetric alkylation was... 

The photocyclization of enamides has been widely employed in the construction of heterocyclic systems the N-acryloyl-2-aminopyridines 37, for example, are converted on irradiation to the lactams 38.36 Numerous benzylisoquinoline alkaloids have been prepared using this approach, and in particular, the syntheses of benzo[c]phenanthridine alkaloids have been reviewed.37 Thus, irradiation of the [Z]-l-ethylidene-2-benzoyltetra-hydroisoquinoline 39 affords the corresponding 8-oxoberberine 4038 competing photoisomerization to the E-isomer is observed but cyclization occurs only via the Z-isomer. Examples of syntheses of Amaryllidaceae and indole alkaloids have also been reported. In this way, the precursor 41 of ( )-lycoran has been obtained by oxidative cyclization of the enamide 42.39... 

---