Deuterated isohumulones can be prepared directly from humulones by an acyloin ring contraction under either magnesium-catalyzed basic conditions or by photochemical-induced reactions in deuterated solvents. Reactions of humulones with biphasic methylene chloride/aqueous NaOD and MgSO4 in D2O leads to stereoselective formation of cis-d
3-isohumulones (cis/trans ratio of 82:18) as the magnesium salts in yields of 71–83%. Greater than 95% incorporation of three deuterons is observed at the C5 position of the pentenone ring and the methylene position of the C4 acyl group. Photochemical isomerization with a 400 nm blue LED source enables stereospecific formation of deuterated trans-isohumulones in 36–82% yield with greater than 95% incorporation of deuterium at the C5 ring position. Oxidation of humulones with cumene hydroperoxide in basic D2O gives isohumulinones with partial 55–73% incorporation of deuterium due to keto–enol isomerization of the methylene substituent of the C4 acyl group. The structural identities of the deuterated products are determined by a combination of negative-mode electrospray mass spectrometry (MS-ESI–) and 2D heteronuclear proton–carbon HMQC NMR analysis.
Key words
humulone - isohumulone - humulinone - deuteration - hydrogen–deuterium exchange - isotopic labeling - heteronuclear proton–carbon NMR
