Neodihydrothebaine and bractazonine, two dibenz[d,f]azonine alkaloids of Papaver bracteatum

Theuns, Hubert G.; Lenting, H.B.M.; Salemink, C. A.; Tanaka, Hitoshi; Shibata, Masayoshi; K, Ito; Lousberg, R. J. J. C.

doi:10.1016/s0031-9422(00)82630-8

Cited by 18 publications

(11 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The compound was eluted with methanol and concentrated to dryness under reduced pressure. Mass spectral and NMR analyses showed identical values compared with authentic neodihydrothebaine (20). Mass spectroscopy (electron impact, at 70 eV) yielded m/z (relative intensity): 313 (100), 256 (62), 255 (40).…”

Section: Product Identificationmentioning

confidence: 77%

“…A minor amount of salutaridinol-7-O-acetate may have escaped or have been transported into the more neutral cytosol where the acetate spontaneously formed the iminium ion of neodihydrothebaine. This intermediate should be easily reduced by NAD(P)H-dependent enzyme systems to neodihydrothebaine, which together with bractazonine is present in this plant at 0.11% (dry weight) (20). Clearly, the dibenz[d,f]azonine alkaloids of this plant have their biogenetic origin in salutaridinol and not in thebaine.…”

Section: Discussionmentioning

confidence: 91%

“…After borohydride reduction, the compound was identified here as the dibenz[d,f]azonine alkaloid neodihydrothebaine synthesized for the first time by Bentley (23) (Fig. 3), which has been also isolated previously as a natural product from P. bracteatum (20). To explain the formation of the imine of neodihydrothebaine from salutaridinol-7-O-acetate at neutral pH, we assume that the migrating carbon atom is exposed to high nucleophilic pressure through the phenolic and methoxy oxygens.…”

Section: Discussionmentioning

confidence: 94%

“…The salutaridinol-7-O-acetate reference was chemically synthesized and rigorously identified ( 1 H NMR) as reported previously (1). Comparison with the enzymatically formed metabolite including mass spectral analysis (electron impact, 70 eV; m/z (relative intensity) ϭ 312 (20), 311 (100), 296 (29)) ensured that both substances were identical.…”

Section: Product Identificationmentioning

confidence: 99%

“…3). This product was identified by comparing its reduction (NaBH 4 ) product with authentic neodihydrothebaine (20) by mass spectral and NMR analyses as described under "Experimental Procedures. "…”

Section: Product Identificationmentioning

confidence: 99%

See 4 more Smart Citations

Acetyl Coenzyme A:Salutaridinol-7-O-Acetyltransferase from Papaver somniferum Plant Cell Cultures:

Lenz

Zenk

1995

Journal of Biological Chemistry

View full text Add to dashboard Cite

Acetyl coenzyme A:salutaridinol-7-O-acetyltransferase, a highly substrate-specific enzyme, has been purified nearly 3,000-fold to homogeneity from Papaver somniferum plant cell suspension cultures. Purification was achieved by fractionated ammonium sulfate precipitation, dye-ligand affinity chromatography on matrex red A, gel filtration, ion exchange chromatography on Mono Q and a second dye-ligand affinity chromatography on fractogel TSK AF Blue. The purified enzyme was a single polypeptide with an M r ‫؍‬ 50,000 displaying an isoelectric point of 4.8, a pH optimum between pH 6 and 9 and a temperature optimum at 47°C. The K m values for the substrate salutaridinol and the co-substrate acetyl coenzyme A were 7 and 46 M, respectively. Salutaridinol-7-O-acetyltransferase catalyzes the stoichiometric transfer of the acetyl group from acetyl coenzyme A to the 7-OH group of salutaridinol yielding salutaridinol-7-O-acetate, which is a new intermediate in morphine biosynthesis. Salutaridinol-7-O-acetate undergoes a subsequent spontaneous allylic elimination at pH 8 -9, leading to the formation of thebaine (1), the first morphinan alkaloid with the complete pentacyclic ring system, or at pH 7 leading to dibenz[d,f]azonine alkaloids that contain a nine-membered ring. Acetylation and subsequent allylic elimination is a new enzymic mechanism in alkaloid biosynthesis, which in the poppy plant can transform one precursor into alkaloids possessing markedly different ring systems, depending on the reaction pH.

show abstract

Section: Product Identificationmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 91%