Total Synthesis of the Galbulimima Alkaloid ( )-GB 13

• Published in: Australian journal of chemistry Vol. 63; no. 5; pp. 742 - 760
• Main Authors: McLachlan, Matthew M.W, O'Connor, Patrick D, Fairweather, Kelly A, Willis, Anthony C, Mander, Lewis N
• Format: Journal Article
• Language: English
• Published: COLLINGWOOD Collingwood, Victoria: CSIRO Publishing 2010; Csiro Publishing
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; POTENT ANTAGONIST; (+)-HIMBACINE; (+)-HIMBELINE; HIMBACINE DERIVATIVES; DIELS-ALDER REACTION; CARBONYL-COMPOUNDS; CHEMICAL CONSTITUENTS; MUSCARINIC RECEPTOR; DIMETHYL-SULFOXIDE; M-2 SUBTYPE
• ISSN: 0004-9425; 1445-0038
• DOI: 10.1071/ch10056

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.