Analogues of amphibian alkaloids: total synthesis of (5R,8S,8aS)-(-)-8-methyl-5-pentyloctahydroindolizine (8-epi-indolizidine 209B) and [(1S,4R,9aS)-(-)-4-pentyloctahydro-2H-quinolizin-1-yl]methanol.

Beilstein Journal of Organic Chemistry
Joseph P MichaelChristiaan W van der Westhuyzen

Abstract

Prior work from these laboratories has centred on the development of enaminones as versatile intermediates for the synthesis of alkaloids and other nitrogen-containing heterocycles. In this paper we describe the enantioselective synthesis of indolizidine and quinolizidine analogues of bicyclic amphibian alkaloids via pyrrolidinylidene- and piperidinylidene-containing enaminones. Our previously reported synthesis of racemic 8-epi-indolizidine 209B has been extended to the laevorotatory enantiomer, (-)-9. Attempts to adapt the synthetic route in order to obtain quinolizidine analogues revealed that a key piperidinylidene-containing enaminone intermediate (+)-28 was less tractable than its pyrrolidinylidene counterpart, thereby necessitating modifications that included timing changes and additional protection-deprotection steps. A successful synthesis of [(1S,4R,9aS)-4-pentyloctahydro-2H-quinolizin-1-yl]methanol (-)-41 from the chiral amine tert-butyl (3R)-3-{benzyl [(1R)-1-phenylethyl]amino}octanoate (+)-14 was achieved in 14 steps and an overall yield of 20.4%. The methodology reported in this article was successfully applied to the enantioselective synthesis of the title compounds. It paves the way for the total synthesis of a ...Continue Reading

References

Apr 1, 2004·Journal of the American Chemical Society·Sape S KindermanFloris P J T Rutjes
Feb 26, 2005·Organic & Biomolecular Chemistry·Joseph P MichaelChristiaan W van der Westhuyzen
Oct 29, 2005·Journal of Natural Products·John W DalyH Martin Garraffo
Feb 3, 2007·Natural Product Reports·Joseph P Michael
Apr 14, 2007·Clinics in Podiatric Medicine and Surgery·Aileen M Takahashi

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Methods Mentioned

BETA
acylation
acetylation

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