Synthesis and odour evaluation of stereoisomers of octahydrobenzopyran derivatives

Abstract

The synthesis and isolation of the four racemic 2,5,5,8a-tetramethyl-3,4,4a,5,6,7,8,8a-octahydro-2H-1-benzopyran stereoisomers from β β β β β -ionone and α α α α α -ionone is reported. It was based on the cyclization of dihydro-β β β β β -ionone and dihydro-α α α α α -ionone with chlorosulfonic acid at low temperature to yield stereospecifically the trans-fused and cis-fused hexahydrobenzopyran derivatives, respectively. The direct cyclization of dihydro-β β β β β -ionol and dihydro-α α α α α -ionol under identical conditions was also explored. In addition to the complete spectroscopic characterization of every isolated isomer, a description of their olfactory properties is displayed. ExperimentalReactions were monitored by gas chromatography (GC) on a Varian CP-3800 gas chromatograph fitted with a methyl silicone (CP-Sil 8 CB) capillary column (30 m × 0.25 mm i.d., film thickness 0.25 µm); carrier gas, He; flow rate, 1 mL/min; oven temperature programme, 50-290°C at a rate of 8°C/min; injector temperature, 250°C; flame ionization detector temperature, 300°C; retention times (R t ) are expressed in minutes; retention indices ( RI) referred to n-alkanes, determined on a DB-5 typephase capillary column according to reference 16. The reaction products were purified by conventional column chromatography (Merck silica gel 60, 70 -230 mesh) or by flash chromatography (Scharlau silica gel 60, 230-240 mesh), in both cases using appropriate mixtures of hexane and Et 2 O.

Discovery of Aromatic Components with Excellent Fragrance Properties and Biological Activities: β-Ionols with Antimelanogenetic Effects and Their Asymmetric Syntheses

“…of (±)-1 and (±)-2, we conducted lipase-catalyzed kinetic resolutions of (±)-1 and (±)-2. First, the screening of suitable lipases was carried out based on the reaction of (±)-1 26) with various commercial lipases in the presence of vinyl acetate in i-Pr 2 O at room temperature. We found that Alcaligenes sp.…”

“…(R)-1 (99% ee) was the largest component, constituting 46% of the product mixture, and therefore, its yield was calculated as 35% from (R)-2. Tetrahydro-β-ionol 29) and dihydro-α-ionol 26) were also found in the mixture as minor components (Chart 2). Although this method still needs improvement in terms of its chemoselectivity, we believe that the asymmetric synthesis of (R)-1 from relatively inexpensive 4 will open up a new pathway to the practical synthesis of optically pure (R)-1.…”

“…The residue was purified by flash column chromatography on silica gel (hexane-EtOAc= 10 : 1) to provide a mixture (153 mg, 77% total yield), in which (R)-1 was found as the largest component. Tetrahydro-β-ionol 29) and dihydro-α-ionol 26) were also found in the mixture as minor products. The GC, GC-MS, 1 H-, 13 C-NMR, and HPLC analysis of the product mixture showed that (R)-1 constituted 46% of the mixute (35% yield from (R)-2) and that its optical purity was 99% ee.…”

“…Lipase-Catalyzed Kinetic Resolution of (±)-1 (Chart 1) A mixture of (±)-1 26) (49 g, 0.25 mol), vinyl acetate (16 g, 0.19 mmol), and lipase QLM (6.0 g, 12 wt%) in i-Pr 2 O (0.63 L) was stirred under a nitrogen atmosphere at room temperature for 4.5 h and filtered using a Celite pad. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (hexaneEtOAc= 30 : 1) to afford (S)-4-(2,6,6-trimethylcyclohex-1-enyl) butan-2-ol [(S)-1] (24 g, 49%, 96% ee) and (R)-4-(2,6,6-trimethylcyclohex-1-enyl) butan-2-yl acetate [(R)-6] (26 g, 45%, 94% ee).…”

“…These compounds might therefore serve as raw materials for whitening reagents in cosmetics. 26) Furthermore, the asymmetric synthesis of (R)-1, which has an excellent floral scent and is expected to serve as a novel fragrance material with high added value, was achieved.…”