Genepolide, a sesterpene gamma-lactone with a novel carbon skeleton from mountain wormwood (Artemisia umbelliformis).
The sesterpene gamma-lactone genepolide (5) has been isolated from a Swiss horticultural variety of mountain wormwood (Artemisia umbelliformis) developed as a thujones-free alternative to native Western Alps wormwoods for the production of liqueurs. Genepolide is the formal Diels-Alder adduct of the exomethylene-gamma-lactone costunolide (2) and the diene myrcene (6), two poorly reactive partners in cycloaddition reactions, and its structure was elucidated through a combination of spectroscopic methods. An investigation on the thermal stability of mixtures of 2 and 6, as well as considerations on the sensitivity of 2 to Brønsted and Lewis acids, suggests that 5 is a genuine natural product and that the Swiss chemotype of A. umbelliformis contains Diels-Alderase enzymatic activity that is lacking in native mountain wormwoods from Western Alps. Remarkable differences in thermal and acid-catalyzed reactions of the cyclodecadiene moiety of 2 and 5 suggest that quaternarization at C-11 has far-reaching effects on the reactivity of their homoconjugated medium-sized diene system. The wide occurrence of this structural motif in sesquiterpenoids makes this issue worth a systematic investigation.
Appendino
Giovanni
G
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Universita del Piemonte Orientale, Via Bovio 6, 28100 Novara, Italy. appendino@pharm.unipmn.it
Taglialatela-Scafati
Orazio
O
Romano
Adriana
A
Pollastro
Federica
F
Avonto
Cristina
C
Rubiolo
Patrizia
P
D019306:Artemisia / Q000737:chemistry*; D007558:Italy; D007783:Lactones / Q000737:chemistry* / Q000302:isolation & purification*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification; D013237:Stereoisomerism; D013729:Terpenes / Q000737:chemistry* / Q000302:isolation & purification*
D007783:Lactones; D012717:Sesquiterpenes; D013729:Terpenes; C548573:genepolide; C002602:costunolide