Selective Synthesis of Deuterated cis- and trans-Isohumulones and trans-Isohumulinones

Abstract

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

Publication History

Received: 16 February 2024

Accepted after revision: 03 July 2024

Accepted Manuscript online:
03 July 2024

Article published online:
22 July 2024

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