Partial Synthesis and Structural Elucidation of the Oxidative Metabolites of Lycopene Identified in Tomato Paste, Tomato Juice, and Human Serum

Abstract

Two oxidative metabolites of lycopene in tomato paste, tomato juice, and human serum have been prepared by partial synthesis from oxidation of lycopene with m-chloroperbenzoic acid (MCPBA) followed by acidic hydrolysis. Extensive 1H and 13C NMR spectroscopy studies of the purified products of these reactions have confirmed that the major oxidation products of lycopene (I) are lycopene 1,2-epoxide (II) and lycopene 5,6-epoxide (III) (tentative assignment). Several diepoxides of lycopene, namely, lycopene 1,2;5,6-diepoxide (IV), lycopene 1,2;5‘,6‘-diepoxide (V), lycopene 5,6;5‘,6‘-diepoxide (VI), and lycopene 1,2;1‘,2‘-diepoxide (VII), which were formed as minor products, were tentatively identified. Whereas lycopene 1,2-epoxide was found to be fairly stable, lycopene 5,6-epoxide underwent cyclization to form a mixture of diastereomeric epoxides A (VIII, major) and B (IX, minor). The trivial names of 2,6-cyclolycopene-1,5-epoxides A (VIII) and B (IX) have been assigned to these compounds with a novel five-membered ring end-group. Hydrolysis of VIII and IX in dilute solutions of sulfuric acid gave an epimeric mixture of 2,6-cyclolycopene-1,5-diols A (X, major) and B (XI, minor). During chromatographic purification on n-silica gel, II and III partially cyclized to 1,16-didehydro-2,6-cyclolycopen-5-ol (XII) and epoxides VIII and IX partially converted to their respective diols, X and XI. In the course of isolation and purification, the oxidation products of lycopene with MCPBA were found to be extremely sensitive to chromatography on n-silica gel and underwent rearrangement to a number of cyclic epoxides and diols. Upon acid treatment of the mixture of lycopene epoxides, a bicyclic diepoxide of lycopene was formed, which was identified as lycopene 1,6;2,5-diepoxide (XIII). Diols X and XI have also been detected at low concentrations in tomato paste, tomato juice, and human serum. All synthetic compounds have been fully characterized by NMR, UV−vis, and MS. Keywords: 1,16-Didehydro-2,6-cyclolycopen-5-ol; 2,6-cyclolycopene-1,5-diol; 2,6-cyclolycopene-1,5-epoxide; lycopene 1,6;2,5-diepoxide; lycopene 5,6-epoxide; lycopene oxidation products; new serum carotenoids; carotenoid metabolites; NMR; HPLC/mass spectrometry