Beery Molecules – part 6, why is humulone an ‘alpha acid’?

Having talked about humulone in a number of the other beery molecules posts, the title of this one poses a question that I actually do not know the answer to – I’m hoping that this post will attract some comments that will help me to understand why the ‘alpha acid’ label makes sense for humulone.

Organic chemistry nomenclature is a minefield. Almost a couple of centuries of the use of different, sometimes conflicting naming systems, historical accidents and perhaps more sinister shenanigans, has led to multiple names being acceptable for nearly all compounds, and this despite there being an incredibly well-established international body in the form of IUPAC, being responsible for such things.

As such, those of us with an interest in such things tend to take the (apparently casual) use of term ‘alpha acid‘ with a pinch of salt, assuming that somehow, and in some way, there must be some logic behind the label that is attached. However, in the case of humulone and the ‘alpha acid’ moniker, it seems (to me at least), a little more unclear than usual. Let’s start by looking at what ‘alpha’ and ‘acid’ usually mean in isolation since these are pretty simple terms to understand.

The ‘alpha’ carbon, is the carbon directly adjacent to a particular functional group. The naming convention extends to beta carbons as well. For example, alpha and beta carbons (relative to the C=O, carbonyl ¬†group) are shown below.

alpha & beta positions

alpha & beta positions

Things can get messy when there are multiple functional groups in a molecule and alpha’s and beta’s become relative to different positions, but in simple terms the system is pretty easy to understand.

The generic carboxylic ‘acid’ functional group is simply -COOH.

Generic acid

Generic acid

However, many other functional groups can have acid character (in as much as they can release H+ ions and have pH’s below 7), which has the potential to confuse. For example, alcohols and phenols (with -OH groups), can, in the correct environments, be acidic.

So, were does this leave us with humulone? Let’s start by looking at the molecule.

Humulone

Humulone

One would think that ‘alpha acid’ would suggest an acid group (-COOH) at an alpha carbon relative to some important functional group. The first thing that we notice is that there are no acid groups present at all, so that theory goes straight out of the window.

So, what about the potential for other functional groups (that are not acids), to act as acids? Well, we see two -OH groups on the six membered ring in the middle of the molecule; one circled in blue, and one circled in neon green. They are potentially the ‘acidic’ groups that we are talking about, but if they are, what are they ‘alpha’, to? The answer to that question is that the neon green circled -OH is alpha to the carbonyl group circled in pale purple, which gives a combo of C=O and -OH, that looks related to a generic carboxylic acid (thanks to @chemtacular for suggesting this). The ‘blue’ -OH might be considered alpha to a C=C, but I seriously doubt it and even if that is the case I have my doubts about its relevance to what we are discussing, here.

The next possibility of the origin of the ‘acid’ part of the name seems to be wrapped up in the theory known as vinylogy, more specifically that of a vinylogous acid. In this case, vinylogy describes the mimicking of ‘normal’ carboxylic acid group (as above), but where the -OH and the carbonyl group are separated by a conjugated system of single and double carbon-carbon bonds.¬†Each of the two polygons (dark green and orange) show an -OH group separated from a carbonyl group with a conjugated system, i.e., a vinylogous carboxylic acid. OK, if that’s relevant, where does the term ‘alpha’ come into play?

The final piece of the puzzle for me is that compounds similar to humulone such as lupulone, also found in hops, are described as ‘beta acids’.

Lupulone

Lupulone

Lupulone has a vinylogous carboxylic acid (in the red square), and two -OH groups that are in beta positions relative to C=O (shown in the purple polygons). Given those ‘beta’ -OH’s relative to C=O, it would appear that the neon green -OH being alpha to the pale purple carbonyl in humulone, would be the most likely source of the ‘alpha acid’ name. Does that make sense? I hope so, but if not, I’m looking for some help here!

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