Piperidine-based natural products

Alkaloids are basic plant natural products that typically have a nitrogen atom as part of a heterocyclic ring system and indeed are classified on this basis. Thus major classes of alkaloids are based on indole, isoquinoline, pyrrolidine, piperidine, pyrrolizidine, quinoline, tropane, quinolizidine or other heterocyclic ring systems. Other alkaloids are basic monoterpenoid, sesquiterpenoid, diterpenoid, steroid, purine, pyrimidine or peptide entities. Some of these compounds are exceptionally toxic [1,6, 7-12]. 

Nitrogen based heterocycles are present in an array natural products, thousands of which have been mentioned in clinical or preclinical studies.1 Thus, the synthesis of piperidine-2 and pyrrolidine-3 derivatives have attracted much attention from the modem day organic chemists. Of particular interest are strategies that lead to chiral heterocyclic derivatives.4... 

It should be noted that several domino reactions exist where the Michael/SN-type processes are reversed. For instance, bicylo[3.3.1]nonane ring systems, applicable as synthons for the construction of various natural products [96], have been synthesized by Srikrishna and coworkers using a domino SN/Michael process [97]. This type of domino reaction was also used by the group of Bunce to synthesize N-pro-tected pyrrolidines and piperidines bearing functionalized side chains at C-2 [98], For a domino alkylation/spiroannulation process to give homoerythrina alkaloids 2-177 [99], Desmaele/dAngelo and coworkers have treated the 2-tetralones 2-179 with 2-180 in the presence of Cs2C03 as base (Scheme 2.42) [100],... 

Harrity and co-workers have developed strategies for piperidine synthesis based on [3+3] cycloaddition reactions and have published a perspective on their and the work of other groups <05OBC1349>. The construction of 6-membered nitrogen heterocycles was included in a review of the [3+3] cycloaddition approach to natural product synthesis by Hsimg and coworkers <05EJO23>. 

In an effort to uncover anticancer active metabolites in Brazilian plants, in early 1993 we initiated active collaboration with several Brazilian natural products chemists. Out of the large number of extracts brought to our laboratory by Dr. Vanderlan da S. Bolzani and screened in our mechanism-based yeast bioassay, extracts derived from two leguminous plants were selected for further studies. Based on preliminary investigation the bioactive methanolic chloroform extract of the leaves of Cassia leptophylla which was shown to contain bioactive alkaloidal constituents was further processed for alkaloids. The alkaloid fraction thus obtained was fractionated by column chromatography on alumina, followed by Silica gel preparative TLC and reversed-phase TLC to afford seven piperidine alkaloids [55] (-)-spectaline (68), (-)-spectalinine (69), canavaline (70), leptophyllin A (71), 3-acetylleptophyllin A (72), iso-... 

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