Total Synthesis of the Galbulimima Alkaloid (±)-GB 13

Matthew M. W. McLachlan; Patrick D. O’Connor; Kelly A. Fairweather; Anthony C. Willis; Lewis N. Mander

doi:10.1071/CH10056

RESEARCH FRONT

Total Synthesis of the Galbulimima Alkaloid (±)-GB 13

Matthew M. W. McLachlan ^A , Patrick D. O’Connor ^A , Kelly A. Fairweather ^A , Anthony C. Willis ^A and Lewis N. Mander ^A ^B

+ Author Affiliations

- Author Affiliations

^A Research School of Chemistry, Australian National University, Canberra, ACT 0200, Australia.

^B Corresponding author. Email: mander@rsc.anu.edu.au

Australian Journal of Chemistry 63(5) 742-760 https://doi.org/10.1071/CH10056
Submitted: 28 January 2010 Accepted: 19 March 2010 Published: 21 May 2010

Abstract

The synthesis of alkaloid GB 13 (4), isolated from the North Australian rain forest tree Galbulimima belgraveana is described. Birch reductive alkylation of 2,5-dimethoxybenzoic acid by 3-methoxybenzyl bromide, followed by an acid-catalyzed cyclization was used to synthesize the [3.3.1]bicyclononane 12. Ring contraction performed on the diazoketone 19 followed by a Diels–Alder reaction generated a pentacyclic intermediate 34 with a carbon skeleton closely resembling the target alkaloid. The surplus nitrile substituent, required for activation and regioselectivity in the Diels–Alder reaction, was removed by treatment with lithium and liquid ammonia. Birch reduction of the aromatic ring could be performed at the same time to give diene 38 and thence enone 41, which was cleaved by means of an Eschenmoser fragmentation. The piperidine ring found in the natural product was formed by reductive cyclization of bis-oxime 49 derived from the alkynyl ketone 48 and the resulting material further elaborated to GB 13.

Acknowledgements

The authors thank the ANU Graduate School (GSS scholarship to M.M.W.M. and P.D.O.) and the Research School of Chemistry (Alan Sargeson Merit Award to M.M.W.M. and P.D.O.) for their generous funding. The authors also acknowledge the skill and commitment of the late Bruce Twitchin in making several advanced intermediates.

References

Total Synthesis of the Galbulimima Alkaloid (±)-GB 13

Abstract

Acknowledgements

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