Dehydrohumulinic acids

P James, T Tynan, I McMurrough, J Byrne. Preparation, purification and separation by high performance liquid chromatography of humulinic acids, dehydrohumulinic acids, and hulupones. J Inst Brew 96 137-141, 1990. 

Irradiation of (6) at 300nm brings about conversion to dehydrohumulinic acid (7) by epimerization at C-4 and (8) via... 

Treatment of cw-humulinic acid with alkali caused it to revert to the trans form the equilibrium mixture consists of over 90% of rra/i -humulinic acid. Oxidation of n>humulinic acid with bismuth oxide also gave dehydrohumulinic acid [79]. This result suggested that the two humulinic acids were epimeric at C-4 and this was confirmed by proton magnetic resonance spectroscopy [79]. Thus in rr AW-humulinic acid (77 or 80 R = H) the C-4 hydroxy group and the C-5 isopentenyl chain have the trans configuration and lie on opposite sides of the planar cyclopentenone ring. In cw-humulinic acid (79 or 81 R = H) both bulky substituents lie on the same side of the ring. All these compounds exist as mixtures of tautomers. 

Bondeel, M. A., D. De Keukeleire, and M. Verzele, The photolysis of rran.s-isohumulone to dehydrohumulinic acid, a key route to the development of sunstruck flavour in beer, J. Chem. Soc. Trans. I, 2715-2717 (1987). 

In direct sunlight or in the presence of photosensitisers (such as riboflavin and polyphenols), the side chain is cleaved, which gives dehydrohumulinic acids (Figure 8.92). Decarbonylation of the formed acyl radical and recombination with a thiol radical, originating from sulfur compounds in beer, yields but-2-en-1-thiol, causing the so-called light-struck off-flavour (Section 8.2.9.1.2). 

Figure 8.92 Formation of dehydrohumulinic acids and 3-methylbut-2-ene-1-thiol from isohumulones.

Rg. 20. Formation of humulinone (24), oxyhumulinic acid (25) and dehydrohumulinic acid (26). 

Treatment of dehydrohumulinic acid with hydrogen perchlorate affords an isomer... 

Moreover, two triplets for two methylene groups occur at 8 1.78 and 8 2.44, respectively. The compound clearly has a dihydropyran ring and is called cyclized dehydrohumulinic acid. No distinction can be made between the alternative structures 144 and 145 (Fig. 68) or the 8-(or 9-)-(1-hydroxy-3-methylbutylidene)-3,3-dimethyI-2-... 

Fig. 68. Structural formulae of dehydrohumulinic acid (26), cyclized dehydrohumulinic acid (144,145), dehydrated humulinic acid (146) and dehydrated cohumulinic acid (147).

Dehydrohumulinic acid (1.34 g 5.08 x 10 mol) In acetic acid (75 ml) is stirred with hydrogen perchlorate (1.5 ml) during 48 h. After dilution with water and extraction with hexane, the cyclized dehydrohumulinic acid is isolated by distillation at 120-130°C and 3 x 10 mm Hg (0.34 g 25%). 

Hulupone is synthesized in 54% yield by alkenylation of the sodium salt of dihydrohumulinic acid (see 8.4.3.1.1.) with 3-methyl-2-butenyl bromide (10). Cohulupone and adhulupone can be prepared similarly (9). However, cohulupone is more easily available from the natural colupulone. A series of analogous compounds has been obtained by reaction of dehydrohumulinic acid with various alkylating reagents (9,10). 

The corresponding acylated compound, which also occurs in the reaction mixture, may be obtained upon prolonged heating of lupulone (or colupulone) in disodium carbonate (9). The troublesome separation of compound 286 (Fig. 114) does not allow isolation of pure material. Periodate cleavage affords dehydrohumulinic acid (see 8.4.4.2.) and 2,8-dimethylnona-2,7-dien-5-one. Compound 286 is 2-(3-methyl-butanoyl)-5-(3-methyl-2-butenyl)-3,4-dihydroxy-4-[1-(3-methyl-2-butenyl)-1-hydroxy-4-methyl-3-pentenyl]-2-cyclopentenone. Isomerized hop extracts with a high level of beta acids contain compounds 285 and 286 (2-3%). 

The chemistry of the humulinic acids is fairly complex. There are cis and trans humulinic acids, partially racemized, humulinic acid C, humulinic acid D, deoxohumulinic acid C, isohumulinic acid, reduced and other derivatives of those already mentioned, oxyhumulinic acids, dehydrohumulinic acid, cyclized humulinic acid and the list is still not complete. LC of all these compounds would probably be worthwhile. 

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