SYNTHESIS AND ENANTIODIFFERENTIATION OF ISOMERIC 2,3,5,6,8,8A-HEXAHYDRO-2,5,5,8A-TETRAMETHYL-7H-1-BENZOPYRAN-7-ONES (3,4-DIHYDRO-3-OXOEDULANS)

The benzopyran derivatives 1a-d mere prepared in a biomimetic type reaction from their presumed natural precursor 3-oxo-retro-alpha-ionol, which was available from alpha-ionone by tert-butyl chromate oxidation, reduction with NaBH4, and subsequent rearrangement of the 7,8 double bond. The so-obtained geometrical isomers of 3-oxo-retro-alpha-ionol (4a/b) were separated by preparative and analytical multilayer coil countercurrent chromatography. Racemic 3-oxo-retro-alpha-ionol (4a) was esterified with (R)-(-)-2-phenylpropionic acid, and the resulting diastereomeric esters (5a/b) were isolated in pure form by preparative HPLC. Configuration at C-9 was determined by H-1 NMR spectroscopy. The isomeric ketols 6a/b obtained from esters 5a/b by enzymatic hydrolysis were subjected to thermal treatment (simultaneous distillation extraction, pH 1), yielding two pairs of diastereomeric 3,4-dihydro-3-oxoedulans (1a/b and 1c/d). The absolute configuration at C-8a was established by NOE experiments. Using on-line coupled multidimensional gas chromatography-mass spectrometry [DB-Wax/octakis(2,6-di-O-methyl-3-O-pentyl)-gamma-cyclodextrin] with selected ion monitoring mode, enantiodifferentiation of 1a-d in a number of natural sources was carried out.