1'-Oxosafrole is a phenyl vinyl ketone metabolite of the allylbenzene safrole.
Human liver produces 1'-oxosafrole as a primary detoxification route of 1'-hydroxysafrole in vitro. On the contrary, in rats this is a minor metabolite of 1'-hydroxysafrole.[1]
1'-Oxosafrole, which is electrophilic, has little or no carcinogenic activity in rats and mice.[2]
Giving 1'-oxosafrole to rats and mice produced 3'-(glutathion-S-yl)-1'-oxo-2',3'-dihydrosafrole and 3'-(N-acetylcystein-S-yl)-1'-oxo-2',3'-dihydrosafrole as metabolites. These conjugates could be synthesized in a lab by non-enzymatic reaction of 1'-oxosafrole with glutathione and N-acetylcysteine at pH 8.[2]
Reactivity
The 2',3'-double bond of 1'-oxosafrole reacts with amines such as dimethylamine, piperidine, and pyrrolidine at room temperature without enzyme catalysts to form the corresponding 3'-addition products leading to alkaloids of potential psychoactivity.[3][5]
The 2',3'-double bond of 1'-oxosafrole reacts with glutathione and N-acetylcysteine at pH 8 without enzyme catalysts to form the corresponding conjugates 3'-(glutathion-S-yl)-1'-oxo-2',3'-dihydrosafrole and 3'-(N-acetylcystein-S-yl)-1'-oxo-2',3'-dihydrosafrole.[2]
P. C. Wislocki. P. Borchert, E. C. Mlller, and J. A. Miller. reported that 1'-oxosafrole (1'-Ketosafrole) reacts with methionine, guanosine, and guanylic acid.[6]
Alkaloid Metabolites
Safrole is proven to produce dimethylamine, piperidine, and pyrrolidine alkaloids as very minor metabolites after oral or topical use. They are believed to be adducts that form as 3'-addition products of 1'-oxosafrole and the endogenous amines dimethylamine, piperidine, and pyrrolidine. They are presumed to be psychoactive, and to contribute to the effects of nutmeg as sassafras.[4]
Dimethylamine Adduct
3-N,N-Dimethylamino-1-(3,4-methylenedioxyphenyl)-1-propanone is the dimethylamine adduct of 1'-oxosafrole.
Piperidine Adduct
3-Piperidino-1-(3,4-methylenedioxyphenyl)-1-propanone is the piperidine adduct of 1'-oxosafrole.
Pyrrolidine Adduct
3-Pyrrolidino-1-(3,4-methylenedioxyphenyl)-1-propanone is the pyrrolidine adduct of 1'-oxosafrole.
Synonyms: 3,4-Methylenedioxyphenyl vinyl ketone; 1'-ketosafrole; 3,4-Methylenedioxyphenylvinyl ketone; 5-Acryloyl-1,3-benzodioxole; 1-(1,3-Benzodioxol-5-yl)-2-propen-1-one;
PubChem Compound ID: 160188
CAS: 30418-53-2
Molecular Weight: 176.16872 [g/mol]
Molecular Formula: C10H8O3
XLogP3: 1.9
H-Bond Donor: 0
H-Bond Acceptor: 3
IUPAC Name: 1-(1,3-benzodioxol-5-yl)prop-2-en-1-one
InChI: InChI=1S/C10H8O3/c1-2-8(11)7-3-4-9-10(5-7)13-6-12-9/h2-5H,1,6H2
InChIKey: LNOUMTOCQWMBOJ-UHFFFAOYSA-N
Canonical SMILES: C=CC(=O)C1=CC2=C(C=C1)OCO2
See Also
- 1'-Oxosafrole-Amine
- 1'-Oxosafrole-DEA
- 1'-Oxosafrole-DMA
- 1'-Oxosafrole-PEA
- 1'-Oxosafrole-Piperidine
- 1'-Oxosafrole-Pyrrolidine
- Nutmeg
- Oilahuasca Activation
- Safrole
- Sassafras