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

Distribution and metabolism of dietary carotenoids in humans as a criterion for development of nutritional supplements

“…Metabolism of lycopene in humans involves epoxidation at the 5,6-position, followed by rearrangement and ring opening to yield 2,6-cyclolycopene-1,5-diols I and II whose structures have been confirmed by partial and total synthesis [36,37] (Fig. 3).…”

Accumulation of Paprika Carotenoids in Human Plasma and Erythrocytes

“…Recently, several oxidative metabolites of lutein, zeaxanthin, and lycopene have been found in humans and other mammals. Lutein undergoes oxidation to ε, ε-carotene-3,3 -dione via 3-hydoxy-β, ε-caroten-3 -one 26 29 , while lycopene is converted to cyclolycopene-5,6-diols and several apolycopeneals 29,30 . These carotenoids are found at very low levels 50 pmol/mL in human plasma 27,28,30 .…”

An Update on the Health Effects of Tomato Lycopene

“…Lycopene-1,2-epoxide and lycopene-5,6-epoxide were identified in tomatoes and tomato products by multiple groups (Britton & Goodwin 1969, 1975; Ben-Aziz et al 1973; Kamber & Pfander 1984; Khachik et al 1992). Later, nuclear magnetic resonance (NMR) research revealed that lycopene-5,6-epoxide had been misidentified and was actually 2,6-cyclolycopene-1,5-epoxide (Khachik et al 1998b). An alcohol derivative, 2,6-cyclolycopene- 1,5-diol, was also identified in tomato products and later found to be present in human blood plasma and breast milk (Khachik et al 1992, 1997, 1998a).…”

“…An alcohol derivative, 2,6-cyclolycopene- 1,5-diol, was also identified in tomato products and later found to be present in human blood plasma and breast milk (Khachik et al 1992, 1997, 1998a). These researchers hypothesized that 2,6-cyclolycopene-1,5-epoxide was converted to 2,6-cyclolycopene-1,5-diol in humans, presumably during digestion, given that none of the epoxide was identified in human samples, and the alcohol is present in small quantities in the food (Khachik et al 1998b). …”