Syntheses and Phytotoxicity of All Stereoisomers of 6-(2-Hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one and Determination of the Effect of the α,β-Unsaturated Carbonyl Structure and Hydroxy Group Bonding to Chiral Carbon.

All four stereoisomers of naturally occurring 6-(2-hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one (1) were synthesized by employing yeast-reduction products with high optical purity [from 95% enantiomeric excess (ee) to more than 99% ee], and then their phytotoxicities against lettuce and Italian ryegrass were evaluated. In the Italian ryegrass seedlings test, (6S,2'R)-1 showed the most potent and stereospecific activity against the shoots (IC50 = 260 μM) and roots (IC50 = 43.2 μM), with a significant difference from other stereoisomers. The highest seed germination inhibitory activity against Italian ryegrass seed was also observed in (6S,2'R)-1, showing a 53% germination ratio from the control at 1000 μM. This advantageous (6S,2'R) stereochemistry was employed in the syntheses of α,β-dihydro, 2'-dehydroxy, and 2'-methoxy derivatives 13-15. By the test using these derivatives, the importance of the α,β-unsaturated double bond and hydroxy group bonding to a chiral center on the 6-alkyl chain of 5,6-dihydro-α-pyrone for phytotoxicity was determined. In the test against lettuce, the 6S configuration and (6S,2'S) configuration were necessary for growth inhibition (IC50 = ca. 60 μM) and germination inhibition (63% germination ratio at 1000 μM), respectively.