Synthesis of alpha-tocohexaenol (alpha-T6) a fluorescent, oxidatively sensitive polyene analogue of alpha-tocopherol.
A polyunsaturated analogue of alpha-tocopherol was synthesized that is both fluorescent and sensitive to peroxidative chemistry that occurs in phospholipid membranes. alpha-Tocohexaenol 1, [(S)-2,5,7,8-tetramethyl-2-((1E/Z,3E,5E,7E,9E)-4,8,12-trimethyltrideca-1,3,5,7,9,11-hexaenyl)chroman-6-ol, alpha-T6] was prepared by condensing a known triene fragment triphenyl-(2,6-dimethyl-octa-2,4,6-trienoic acid methyl ester)-phosphonium bromide with a protected chromanol aldehyde, (2S)-6-{[tert-butyl(dimethyl)silyl]oxy}-2,5,7,8-tetra-methyl-3,4-dihydro-2H-chromene-2-carbaldehyde. The full side chain was then completed with isopentyl(tri-n-butyl)phosphonium bromide to give 1. The geometry of the C1'-C2' alkene appears to be Z (cis) although the coupling constants of the olefinic protons are intermediate between values normally assigned to E and Z-isomers. In ethanol, alpha-T6 has a maximum absorption at 368nm with an absorption coefficient of 45,000M(-1) cm(-1), and displays a maximum fluorescence emission at 523nm. The susceptibility of alpha-T6 to peroxidative chemistry was dependent on the concentration of azo-initiators of lipid oxidation in acetonitrile solution as well as in phospholipid vesicles. A loss of fluorescence at 520nm was observed when alpha-T6 (vesicles or alpha-T6-lipid mixtures) was exposed to peroxidative conditions, and this loss mirrored the production of conjugated dienes and trienes during the peroxidation of bulk phospholipids. Addition of natural alpha-tocopherol during the AMVN induced oxidation of 4microM alpha-T6 and 0.5mg/ml soybean PC induced a characteristic lag phase, after which the fluorescence of alpha-T6 began to lessen. Thus, alpha-T6 may be a useful reporter not only of tocopherol location in cells, but also of the extent of peroxidative events.
Wang
Yongsheng
Y
Toronto Research Chemicals, Inc., 2 Brisbane Rd., North York, ON, Canada M3J 2J8.
Panagabko
Candace
C
Atkinson
Jeffrey
J
D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry; D005453:Fluorescence; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D011090:Polyenes / Q000737:chemistry*; D013237:Stereoisomerism; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
C548622:(S)-2,5,7,8-tetramethyl-2-((1E 1Z3E,5E,7E,9E)-4,8,12-trimethyltrideca-1,3,5,7,9,11-hexaenyl)chroman-6-ol; D002839:Chromans; D011090:Polyenes; D024502:alpha-Tocopherol