Interesting facts from the world of organic chemistry
Alkanes and cycloalkanes:
Adamantane
Adamantane is the trivial name of a chemical compound with the general formula C10H16, but with a unique carbon skeleton with the systematic name tricyclo[3.3.1.13,7]decane. It is a solid substance forming colorless crystals with a camphor smell. The carbon atoms are distributed in space similarly to the carbon atoms in a diamond (hence the name for the more complex adamantanes called diamantes). It naturally follows that the molecule is very symmetrical, which is manifested not only by crystallization in the cubic system, but practically especially by a very high melting temperature (around 270 °C in a sealed capillary), which is generally several tens of °C higher than common for alkanes of the same molar mass. Sublimes in real conditions.
The first mentions of it date back to the first decades of the last century, when its existence was predicted. This was followed by the first unsuccessful attempt to synthesize an adamantane skeleton in 1922. The continuing sequence of several unsuccessful attempts to prepare substances with an adamantane skeleton was completed many years later by its first accidental isolation from Hodonín oil by Czech chemists (oil with an adamantane content in the range of 0.2-0, 3%, i.e. 33 kg of crude oil had to be processed to obtain 100 g). But then the Second World War broke out and all work was suspended.
However, after the World War II adamantane lull, there was a massive surge in interest in this compound caused by the discovery of the virostatic effects of 1-adamantylamine in the mid-1960s. This started a literal marathon about possible applications of the adamantane group, which culminated at the turn of the millennium with the discovery of adamantane derivatives in recent plant material. Until then, the premise was that the described skeleton could not be the fruit of living nature.
Today we already know that, for example, the well-known fish toxin of the genus Fugu tetrodotoxin and the very similar chirikvitoxin from frogs of the genus Atelopus are essentially substituted heteroadamantans. Also, the adamantane skeleton has so far been demonstrated in representatives of two genera from the Guttiferae family, which also includes our St. John’s wort.
Returning to the extraction of adamantane from oil, it must be clear to us that its isolation from this increasingly scarce resource combined with rising energy prices would be quite costly. It was necessary to assemble a complex of reactions for direct synthesis. After a series of pitfalls and the development of a set of direct synthesis methods, the production process based on the isomerization of tetrahydrodicyclopentadiene with aluminum chloride is currently the most widely used, despite the fact that the yield of the reaction is doubled with the use of the AlCl3 + HCl mixture.
Picture above: Brief scheme of the industrial synthesis of adamantane.
The use of adamantane, as already outlined, falls under medicinal chemistry. More precisely, its derivatives are used – both simple and structurally altered. Simple derivatives include the aforementioned 1-adamantylamine (amantadine), as well as adapromine and rimantadine. These show virostatic effects against influenza A and B viruses. The mechanism of action is quite interesting, as these substances do not eliminate viruses by direct action, but only inhibit the decapsidation phase of viral reproduction (the phase of exposing the genome) and thus provide a sufficiently long time to mobilize the organism’s immunity. Structurally altered, i.e. modified simple without touching the original active sites, include, for example, diadon. These substances can show not only virostatic, but also anti-cancer, hypoglycemic or antidepressant effects.
Resources:
1) VÍCHA Robert and Milan POTÁČEK: Chemické Listy 98, 68 – 74 (2004).
2) VÍCHA R.: Dissertation thesis. Masaryk University, Brno 2005.