Alanine and Phenylalanine

Alanine was one of the few amino acids to be produced synthetically before it was discovered as part of proteins. It was first synthesised in 1850 by the German chemist Adolph Strecker, who was trying to make lactic acid from acetaldehyde, after Justus Liebig had shown the reverse reaction to be possible.1,2 He did manage to produce lactic acid, “but not in the simple way that was expected, but in a detour which, however, led [him] to the discovery of a body that was in various respects not uninteresting”.1

In what would later become known as “The Strecker Synthesis”, Strecker mixed acetaldehyde (then just known as aldehyde, which is important) with ammonia, hydrogen cyanide and hydrochloric acid…

“…and what remains is a strongly acidic, mother liquor which contains the hydrochloric acid compound of a new body which I will call alanine”1

Unhelpfully, Strecker did not give any explanation for the name given to his newly discovered compound, so assumptions have had to be made.

It is generally accepted that the “al-” comes from aldehyde, the key starting material in the reaction. However, the pervading theory for the “-an-“ part is a little vaguer: it is believed to have been added before “-ine” simply for ease of pronunciation. This does make some sense, as “aline” does sound a bit rubbish (no disrespect meant to anyone called Aline, it works much better as a people name than a chemical name). Without confirmation of this from the author, or at least around the same time, I find this explanation a little unsatisfying, but have not been able to find any alternative suggestions. That being said, I do have my own theory.

While I think it is reasonable that Strecker would want to add something into the name between al- and -ine, I couldn’t quite accept that the -an- was just a random syllable. There must have been some inspiration for it, even if it was subconscious, and what better place to take this from than another component of the reaction: cyanide?

The first argument I could see against this hypothesis was that there are more than these two components needed in this reaction: aldehyde, ammonia, hydrogen cyanide, hydrochloric acid, and water (see Wikipedia for the full reaction mechanism). Although, Strecker did not know then what we know now about how this reaction works. It is clear from the equation he proposes that (see an extract from the paper below) that he did not consider the ammonia or acid to be important. Nobody is going to name a compound after the solvent it is made in, so is it the aldehyde and hydrogen cyanide that he considered the key ingredients.

Figure 1. An extract from Strecker’s manuscript illustrating his proposed equation for the synthesis of alanine.1

The second argument against this hypothesis is apparent when looking at the equation above (moving quickly past the fact that they hadn’t quite figured out atomic weights yet). For my theory to work, the German word for hydrogen cyanide used as the time would need to contain the -an- fragment, but here the second named reactant is ‘blausäure’. On seeing this I did think my theory was dead in the water. However, I have selected the extract to include here carefully: you will notice in the text above the equation the word ‘Cyanwasserstoff’. This was, and still is, the German for hydrogen cyanide, while blausäure is the German name given the hydrogen cyanide in water (hydrocyanic acid in English). The first part of both of these names mean blue in English, cyan being from the Greek for blue, cyanos. This can be traced back to isolation of cyanide-based compounds from blue pigments: either Prussian blue or Berlin blue depending on what you read (unravelling that one is a task for another time).

Translated, the text in the extract above reads:

“The alanine is formed by combining equal equivalents of aldehyde and hydrogen cyanide, with the occurrence of 2 equivalents of water, according to the following equation”

So based on this, I stand by my theory of one syllable coming from each reaction component.

Figure 2. My theory for the etymology of alanine.
German names are given in italics with English names in brackets.

With the naming of alanine cleared up (potentially) the naming of another of the amino acids becomes quick to explain: phenylalanine. This compound was given this name in 1882, 6 years before alanine was first shown to be a component of proteins.2 The German chemists Erlenmeyer and Lipp performed the Strecker reaction on phenylacetaldehyde (phenyläthylaldehyd in German) to produce phenyl-α-aminopropionic acid.2,3

Within the body of their manuscript they only refer to this compound by the systematic name, and only include their proposed shortening “phenylalanin” in brackets in the title;3 how very casual! It is reasonably clear that they saw the analogy of their reaction with phenylacetaldehyde with the synthesis of alanine from acetaldehyde and named their compound accordingly…a footnote would have been nice though!

References

1.          Strecker A. Ueber die künstliche Bildung der Milchsäure und einen neuen dem Glycocoll homologen Körper. Justus Liebigs Ann Chem. 1850;75:27-45. doi:10.1002/jlac.18500750103

2.          Vickery HB, Schmidt CLA. The History of the Discovery of the Amino Acids. Chem Rev. 1931;9(2):169-318. doi:10.1021/cr60033a001

3.          Erlenmeyer E, Lipp A. Ueber Phenyl-α-amido-propionsäure (Phenylalanin). Berichte der Dtsch Chem Gesellschaft. 1882;15:1006-1007.

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