Pyrrole-indolizidine alkaloids

The venom of ants of the genus Myrmicaria is made up of indolizidine or pyrrole-indolizidine alkaloids [188,189]. The synthesis of some of these alkaloids has already been reported in the review of Leclercq et al. [114]. Thus, we will report here only on the syntheses published since 1999. 

An indolizidine alkaloid isolated from the rhizomes of Polygonatum sibiricum (Liliaceae) also has some unusual features 311). The unnamed alkaloid, for which the structure 326 has been proposed on the basis of good spectroscopic data (IR, UV, MS H, C and HETCOR NMR), is the first 5,6,7,8-tetrahydroindolizine (cyclohexa[a]pyrrole) to have been found as a natural product. In addition, the ethoxymethyl substituent is unique, at least among the natural indolizidines. It should also be pointed out that simple indolizidine alkaloids have never before been isolated from liliaceous species. Although the structure 326 appears to be reasonable in the light of the spectroscopic evidence, judgement should perhaps be reserved until it can be confirmed independently. 

The intramolecular trapping by a pyrrole has been used in a short synthesis of tashiromine 6.360, an indolizidine alkaloid (Scheme 6.131). The optically pure cobaloxime complex 6357, generated from the corresponding alcohol 6.356, was directly trapped by the pyrrole with overall retention of stereochemistry. Reduction of the pyrrole and conversion of the carbon-cobalt bond to a carbon-oxygen bond yielded the alkaloid 6.360 and its diastereoisomer. Another synthesis of this alkaloid may be found in Scheme 2.122. 

Tables I through VIII summarize the occurrences of alkaloids from ants and other insects. Each table presents chemical structures as well as specific sources of particular types of alkaloids e.g.. Table I covers piperidines and pyridines. Table II, pyrrolidines, pyrroles, and indolizidines.

The Aspidosperma family of indole alkaloids has inspired many synthetic strategies for the construction of their pentacyclic framework of the parent compound aspidospermidine (366), since the initial clinical success of two derivatives, vinblastine (10) and vincristine, as anticancer agents. The alkaloids such as (-)-rhazinal (369) and (-)-rhazinilam (6) have been identified as novel leads for the development of new generation anticancer agents [10,11]. Bis-lactams (-)-leucunolam (370) and (-t-)-epi-leucunolam (371) have bio-genetic and structural relationships with these compounds [236]. Recently, enantioselective or racemic total syntheses of some of the these natural product were achieved. One successful synthesis was the preparation of the tricyclic ketone 365, an advanced intermediate in the synthesis of aspidospermidine (366), from pyrrole (1) (Scheme 76) [14]. The key step is the construction of the indolizidine 360, which represents the first example of the equivalent intramolecular Michael addition process [14,237,238]. The DIBAL-H mediated reduction product was subject to mesylation under the Crossland-... 

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