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I should like to know roughly how the hormone melotonin is synthetically made for the pharmaceutical industry (i.e. not how it is made in living beings). I can't seem to find any reference to its manufacture on the web, it is seen to have a fairly simple structure on its Wiki page and biologically it is synthesised from the forerunner amino acid tryptophan. So I believe it is likely to be readily synthesised for use in pharmaceuticals without the use of animal products, but I cannot confirm this.

Specifically, a close relative of mine has been prescribed melotonin and I want to confirm that this substance is not made from animal products, as I live in a country where the authorities in their great wisdom have deregulated the food and meat processing industries. Astoundingly, they did this at exactly the same time that a UK royal commission recommended re-regulation of the same to prevent contamination of food and pharmaceuticals by the Creutzfeld-Jacob prion.

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    $\begingroup$ I don't wish to be argumentative, but even if someone can provide details of a fully synthetic industrial production route, what guarantee does that provide that the manufacturer you're specifically dealing with uses that route? $\endgroup$
    – Greg E.
    Jun 6 '14 at 11:08
  • $\begingroup$ @GregE. None, just gathering evidence to get me one step from a state of complete to partial ignorance: an answer of how it is generally done changes conditional probabilities $\endgroup$
    – Selene Routley
    Jun 6 '14 at 12:55
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    $\begingroup$ Fair enough. You may find these useful: 1, 2. The first is an overview of some synthetic strategies, the second is an EMA report on Circadin (a sustained-release melatonin formulation) which describes a synthesis starting from 5-methoxytryptamine. To my (admittedly limited) knowledge, amino acids (and relatives) are rarely produced by extraction methods these days, but rather by enzymatic and semi-synthetic routes. $\endgroup$
    – Greg E.
    Jun 6 '14 at 13:17
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    $\begingroup$ There's also another document pertaining to Circadin, this one from the Australian Dept. of Health, describing the same synthetic method. If you do a search on tryptamine production, you'll find bacterial and enzymatic routes described, which (to my knowledge) is in line with trends for production of these sorts of compounds. I haven't found a source describing the production of the 5-methoxy derivative specifically, but the synthesis from tryptamine would be a simple one, and I find it unlikely that extraction methods would be used. $\endgroup$
    – Greg E.
    Jun 6 '14 at 13:58
  • $\begingroup$ @GregE. I think whenever you like, you might post an answer to this.... $\endgroup$
    – M.A.R.
    Mar 24 '15 at 12:08
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I do not know the exact process in industry, but these are the steps that I thought of (someone likely thought of this before me, it is a very simple synthesis). The main synthesis of the ring is done in Fischer indole conditions. Therefore I broke up the molecule into a compound known as 4-acetamidobutanal and p-hydrazinoanisole. The first compound is an amide that is available from the reaction of 4-aminobutanal and acetyl chloride or acetic anhydride in the presence of a base. The latter compound is available from the reaction of p-anisidine with sodium nitrite and hydrochloric acid to form the diazonium chloride, and then reduction with sodium sulfite and sodium hydroxide. This is just an example of a synthesis. The overall synthesis shouldn't be more than 5 or 6 steps.

I found an article highlighting the syntheses, you can take a look. Apparently the synthesis that I described above is very similar to the most effective synthesis, a one-pot synthesis done in very similar conditions and having similar starting materials.

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