The total synthesis of the Galbulimima alkaloid GB 13.
This contribution describes a synthetic approach to alkaloid GB 13, previously isolated from the North Australian and Papua New Guinean rain forest tree Galbulimima belgraveana. A 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 8. A ring contraction performed on the diazo derivative 9 of the [3.3.1]bicyclononane led to [3.2.1]bicyclooctane 10. This [3.2.1]bicyclooctane was converted into a dienophile and subjected to a Diels-Alder reaction to generate a pentacyclic intermediate 13 with a carbon skeleton closely resembling the target alkaloid. The surplus substituent, required for activation and regioselectivity in the Diels-Alder reaction, was removed using Birch reductive conditions to effect a decyanation. It was discovered that a Birch reduction of the aromatic ring also present in the molecule could be performed at the same time to give the enone 15, which was cleaved by means of an Eschenmoser fragmentation. The piperidine ring found in the natural product was formed by reductive cyclization of the bis-oxime 18 derived from the alkynyl ketone 17 and the resulting material further elaborated to GB 13 (1) via ketone 20.
Mander
Lewis N
LN
Research School of Chemistry, Australian National University Canberra, A.C.T. 0200, Australia. mander@rsc.anu.edu.au
McLachlan
Matthew M
MM
D000470:Alkaloids / Q000138:chemical synthesis*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D007659:Ketones / Q000138:chemical synthesis*; D010946:Plants, Medicinal / Q000737:chemistry; D014197:Trees / Q000737:chemistry
D000470:Alkaloids; D006576:Heterocyclic Compounds, 4 or More Rings; D007659:Ketones