Carvone hydrogenation mechanisms

Absorption, metaboHsm, and biological activities of organic compounds are influenced by molecular interactions with asymmetric biomolecules. These interactions, which involve hydrophobic, electrostatic, inductive, dipole—dipole, hydrogen bonding, van der Waals forces, steric hindrance, and inclusion complex formation give rise to enantioselective differentiation (1,2). Within a series of similar stmctures, substantial differences in biological effects, molecular mechanism of action, distribution, or metaboHc events may be observed. Eor example, (R)-carvone [6485-40-1] (1) has the odor of spearrnint whereas (5)-carvone [2244-16-8] (2) has the odor of caraway (3,4). 

Catalytic Experiments. Activities were performed in a 1 liter Parr reactor. A typical experiment was performed as follows at a temperature of 100 °C, 100 mg of the catalyst and 1.5 /. wt of (-)-carvone (Aldrich) in n-hexane solution (100 ml) were Introduced in a high pressure Parr reactor equipped with mechanical stirring and automatic temperature control. Before introducing the hydrogen the system was purged 2 or 3 times with Nz> The total hydrogen pressure was 21 atm. The reaction products were analysed by gas chromatography. NMR and Mass Spectrometry and identified as unreacted carvone, carvotanacetone, carvomenthone and three carvomenthol stereoisomers (axial-equatorial, equatorial-equatorial and equatorial-axial). 

Photosynthetic microorganisms and plant cell cultures are very important sources of enzymes for the reduction of olefins151, 2981. For example, Hirata et al. found that reduction of enone 11 with Nicotiana tabacum p90 reductase and Nicotiana tabacum p44 reductase affords (S)- and (R)-alkylcyclohexanones, respectively, with excellent enantioselectivities as shown in Fig. 15-53. They also found two enone reductases from Astasia longa, a nonchlorophyllous cell line classified in Euglenales, and studied the mechanism. Both catalyzed enantiospecific trans-addition of hydrogen atoms to carvone from the si-face at the a-position and from the re-face at the p-position. 

With regard to the metabolism of primary carotenoid degradation p ucts, recent results obtained by Tang and Suga (57) have indicated a two-step mechanism for the conversion of the primary carotenoid metabolite B-ionone 1 to 14 in Nicotiana tabacum plant cells (cf. Fig. 4). These results revealed, that first of all, the side-chain double bond is hydrogenated by the action of carvone reductase (co-factor NADH), before the carbonyl function is enzymatically reduced in the second step. Importantly, the enantioselectivity of the latter reductase is decisive for the enantiomeric composition in fruits as outlined for theaspirane formation from the labile precursor diol 12 (cf. Fig. 5). The formation of vitispiranes 10, edulans 11 and related Ci3-norisoprenoids (29,30) is known to proceed via similar mechanisms. 

Since the reaction is taking place within the (chiral) active site of the enzyme, the reaction mechanism is stereospecific, the addition of H2 occurring with antistereochemistry. There is only one exception reported, the syn-hydrogenation of verbenone, carvone, and cyclohex-2-enone catalyzed by OYE of Nicotiana tabacum (Scheme 2.3) [12]. However, the aforementioned tremendous advances in molecular biology and biotechnology will facilitate recombinant expression and synthetic use of these novel biocatalysts by protein engineering. In this respect, recent examples already report structure-driven mutagenesis, which successfully improved reaction specificity or enantioselectivity [13,14]. 

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