Alkaloid syntheses center formation

Marks et al. [77, 294]. The formation of heterocyclic nitrogen compounds is of relevance in natural products, particularly in alkaloid synthesis, when the formation of the C-N bond occurs with asymmetric induction. The cyclization is not restricted to primary amines and produces 2-methylheterocycles (5-, 6-, 7-membered) with >99% regioselectivity and a new asymmetric center adjacent to the heterocyclic nitrogen atom (Scheme 17). 

We view acetylenic sulfoxide 1 as a two-carbon synthon in alkaloid synthesis. Our general approach, as depicted in Scheme 4, called for a Michael addition of Nu1 to the terminal acetylenic position followed by a cyclization by Nu2 (an intramolecular second Michael addition). This Michael addition cyclization step will build up the basic skeleton of the alkaloid system and at the same time control the absolute stereochemistry of the newly created chiral center through asymmetric induction of the chiral sulfoxide moiety. Finally, the sulfoxide can be transformed to another functional group (X) or used to promote the formation of another bond with Nu3 via trapping of the sulfenium ion intermediate under Pummerer rearrangement conditions (Scheme 4). 

E. FORMATION OF QUATERNARY CARBON CENTERS E.i. Spirocyclizations and Alkaloid Synthesis... 

Narciclasine (215) is an antitumor agent which exerts an antimitotic effect during metaphase by immediately terminating protein synthesis in eukaryotic cells at the step of peptide bond formation (97,101,141,142), apparently by interaction with the ansiomycin area of the ribosomal peptidyl transferase center (142). The alkaloid has also been found to inhibit HeLa cell growth and to stabilize HeLa cell polysomes in vivo (97). Although DNA synthesis was retarded by narciclasine, RNA synthesis was practically unaffected (97,142). Sev-... 

The synthesis of alkaloids described above is based on the generation of a cationic center at the position a to the nitrogen atom of an amide followed by a carbon-carbon bond formation at the a-position as the key reaction. On the other hand, developing an anionic center at the a-position of the N-acylamine generally requires a very strong base which may bring about undesirable side reactions. However, the formation of... 

Studies directed toward the synthesis of amaryllidaceae alkaloids provide instructive examples of the combined use of spirocylization and Michael addition pathways in phenolic oxidations (03MI1). For example, treatment of the norbelladine derivative 164 with BTIB leads, by way of C,C-bond formation, to the spiroannulated azepine 165 (Scheme 47) (96JOC5857, 98JOC6625). Hydrolysis of the amide moiety in 165 results in Michael addition of the nitrogen center to the dienone ring and affords ( )-oxomaritidine (166). BTIB-oxidation of the appropriate... 

Intramolecular insertion into an exocyclic trisubstituted alkene was employed by Grigg and co-workers to construct a quaternary center in their total synthesis of the Amaryllidaceae alkaloid derivative (—)-crinane (44) [13]. Cyclization of aiyl iodide 41 using tri-o-tolylphosphine as ligand afforded a 20 1 mixture of trans and cis tricyclic products 42 and 43 in good yield. Predominant formation of the trans ring juncture observed in this example is unusual. 

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