Date of Award
2008
Degree Type
Thesis
Degree Name
Doctor of Philosophy
Program
Chemistry
Supervisor
Prof. Michael Kerr
Abstract
The herbindole and trikentrin indoles constitute a unique class of cyclopent[g]indoles. These compounds pose a significant synthetic challenge in that the more reactive 2- and 3- positions of the indole are unsubstituted. The initial synthetic approach towards herbindole B centered on an iterative Diels-Alder strategy with a monoamine quinone dienophile leading to a tetracyclic intermediate. Plieninger indolization afforded a suitably substituted indole for elaboration to the natural product. A revised approach towards the related herbindole A and cis-trikentrin A relied on crosscoupling reactions to install the requisite alkyl substituents on the benzenoid portion of the indole. By employing a more elaborated dienophile in the Diels-Alder cyclization, a one-pot protocol was possible for direct conversion to the desired indole intermediate. A selective iodination at the 4-position of the indole provided a suitable handle to install the 4- methyl or 4-ethyl groups of the corresponding natural products via Stille or Negishi couplings. Similarly, triflation of the 5-position oxygen allowed for installation of either a 5-methyl group through a Stille coupling or hydrogenolysis in the case of cis-trikentrin A. In this manner, a divergent synthesis ofthese indole natural products has been completed in 14-19 synthetic steps. A Stereodivergent synthesis of pyrrolidines based on an annulation of an alkoxylamino-tethered cyclopropane with an aldehyde has been developed. Altering the order of addition of catalyst and substrate leads selectively to either a 2,5-trans- or cis-substituted Pyrroloisoxazolidine adduct. Subsequent N-O bond cleavage then reveals the pyrrolidine ring. In this manner, access to both 2,5-trans- and 2,5-cis-pyrrolidines is possible with excellent diastereoselectivity. The method has been applied towards the iii total synthesis of (-)-quinocarcin and construction of the pyrrolidine ring of the natural product is accomplished in a highly efficient one step reaction.
Recommended Citation
Jackson, Stephen K., "The Synthesis of Complex Heterocyclic Natural Products: (±)-herbindole A, B, (±)-cis-trikentrin A and (-)-quinocarcin" (2008). Digitized Theses. 4442.
https://ir.lib.uwo.ca/digitizedtheses/4442