title: Differential reactivity of purified bioactive coffee furans, cafestol and kahweol, with acidic nitrite: product characterization and factors controlling nitrosation versus ring-opening pathways.
abstract: Cafestol and kahweol, coffee-specific furan diterpenes, are believed to cause various physiological effects in human subjects, including an increase in cholesterol and plasma triacylglycerol levels as well as cancer chemopreventive effects. Despite the increasing interest in these compounds raised by the diverse range of biological activities, their reaction behavior and degradation pathways under physiologically relevant conditions remain uncharted. Herein, we report a detailed investigation of the structural modifications suffered by cafestol and kahweol in the presence of acidic nitrite under conditions mimicking those occurring in the stomach during digestion as well as by action of other oxidants. Prior to the chemical study, an isolation procedure for kahweol from green coffee beans was developed based on Soxhlet extraction followed by preparative HPLC. Preliminary experiments showed that kahweol is much more reactive than cafestol toward nitrite at pH 3, as evidenced by inhibition experiments with the 2,3-diaminonaphthalene assay as well as by product analysis in coffee extracts. When exposed to equimolar nitrite in phosphate buffer, pH 3, kahweol gave as a main product the ring-opened dicarbonyl derivative 1. Under more forcing conditions, cafestol reacted as well to give a main nitrogenous product identified as the 1-hydroxy-2-pyrrolinone 2. It is concluded that the conjugated double bond in kahweol is a critical structural element, increasing the susceptibility of the furan ring to protonation rather than nitrosation and favoring ring-opening routes driven by the irreversible oxidation steps. These results offer a useful background to assess the effects of coffee-specific lipids in association with abnormally high nitrite levels from the diet.
authors.affiliation: Department of Organic Chemistry and Biochemistry and Centro Interdipartimentale di Metodologie Chimico-Fisiche, University of Naples Federico II, Via Cinthia 4, I-80126 Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: De Lucia
authors.forename: Lucia
authors.initials: L
authors.lastname: Panzella
authors.forename: Dominique
authors.initials: D
authors.lastname: Melck
authors.forename: Italo
authors.initials: I
authors.lastname: Giudicianni
authors.forename: Andrea
authors.initials: A
authors.lastname: Motta
authors.forename: Alessandra
authors.initials: A
authors.lastname: Napolitano
authors.forename: Marco
authors.initials: M
authors.lastname: d'Ischia
mesh_terms: D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003069:Coffee / Q000737:chemistry; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D005663:Furans / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009573:Nitrites / Q000737:chemistry*; D014280:Triglycerides / Q000097:blood
chemical_list: D003069:Coffee; D004224:Diterpenes; D005663:Furans; D009573:Nitrites; D014280:Triglycerides; C053401:kahweol; D002784:Cholesterol; C053400:cafestol