How to Remember Iridoid Formulas

     The second rule –
     the reward awaits the hero.

   The main thing you should know about iridoids is that all of them necessarily contain a pyranose ring (remember glucose!), but partially dehydrated (that is, with one double bond). This bond in all iridoids is located from the neighboring carbon atom with oxygen to another carbon atom.
   Most iridoids also have a cyclopentane ring, which can also be partially dehydrated; in others, an oxygen atom can be incorporated into this ring, thus turning it into a second pyranose.
  All iridoids that you need to memorize, except for valepotriates, are glycosides, with the glycosidic part represented by glucose (= glycosides); valepotriates, on the other hand, contain residues of isovalerenic acids and are complex esters.
  Cyclopentane iridoids are so named because their second ring is cyclopentane.

  Cyclopentane pyran

  Let’s start with aucubin, as it is first alphabetically, and among those iridoids you need to know, it apparently has the simplest structure. Only it and valtrate, which we will consider among the valepotriates, have a partially dehydrated cyclopentane ring. That is – the dehydrated iridoid is our very first.
  Aucubin contains 2 –OH groups in the cyclopentane ring – one opposite the other: the upper group is independent, while the lower one is part of –CH₂OH.

  Aucubin

  If in the molecule of aucubin the double bond in the cyclopentane ring is broken and an oxygen atom is incorporated into it, thus forming a new three-membered lactone ring, such a cyclopentane iridoid is called catalpol.

  Catalpol

  Another cyclopentane iridoid – loganin – has adjacent –OH and –CH₃ groups in the cyclopentane ring, and in the pyranose ring, besides the oxygen atom, which I hope you are already familiar with from the first two iridoids, to which a glucose residue is attached, there is a –COOCH₃ group (that is, do not forget – in the lower part of the pyranose ring – 2 oxygen atoms and in the upper part – 2 oxygen atoms).

  Loganin

  When the cyclopentane ring is opened between the adjacent –OH and –CH₃ groups with their parallel dehydration (the groups =O and =CH₂ are formed, respectively), loganin turns into a secoiridoid secologanin. Here we will immediately say that secoiridoids are iridoids with an opened cyclopentane cycle.

  Secologanin

  The remaining two secoiridoids that we will consider – sverozid and genciopicroside (= genciopicrin) – are very similar to each other in structure and differ only by the presence or absence of one double bond. They do not have a cyclopentane ring, but instead contain another pyranose. Their lower part is the same as that of secologanin, while in the upper part there is a second pyranose ring, which has a carbonyl group next to the heteroatom O. That is, both sverozid and genciopicrin have 2 oxygen atoms in both the upper and lower parts of the molecule (remember loganin?).

  Sverozid        Genciopicroside
(= Genciopicrin)
 
  In genciopicroside, the upper pyranose ring is unsaturated (one double bond located parallel to the double bond in the lower pyranose ring) unlike sverozid. This can be remembered by analogy with aucubin (first alphabetically and has an unsaturated ring; and genciopicroside is also alphabetically positioned earlier compared to sverozid).
 
    Iridoids of the Valerianaceae family – valepotriates – belong to cyclopentane iridoids.
    The name “valepotriates” can be broken down into three components, telling us that, firstly, they are iridoids of the valerian family (val-); secondly, that they necessarily have an epoxide group (-epo-), and thirdly, about their triester nature (three times complex esters; -triates).
  Valepotriates differ in the degree of saturation of the cyclopentane ring and the nature of the isovalerenic acid residues (isovalerenic and acetoxyisovalerenic), which are attached to the cyclopentane pyran skeleton at positions C₁ and C₇.
  If both isovalerenic acid residues are attached at C₁ and C₇, such compounds are called valtrates; if at C₁ – isovalerenic acid, and at C₇ – acetoxyisovalerenic acid, they are called valepotriates.

  It is easy to remember that dihydrovaltrate is a doubly hydrated valtrate, that is, in the first there is no double bond in the cyclopentane ring, while in the second there is. The same can be said about dihydrovalepotriate and valepotriate.

  Two more common features of the structure of all valepotriates are:

• the presence of a “triangle” – a three-membered heterocyclic ring attached at one of the corners at position C₈;
• a chain –CH₂–O–CO–CH₃ at position C₄, which can be viewed as an acetoxy group –O–CO–CH₃ (which we will remember later), attached to the edge methyl group –CH₃ of the pyranose ring, which thus turns into a –CH₂ group as part of the overall chain.

R₁ = R₂ = isovalerenic acid         – Dihydrovaltrate;

                                                           R₁= isovalerenic acid;
                                                           R₂= acetoxyisovalerenic acid     – Dihydrovalepotriate
 
  You only need to memorize the formulas of isovalerenic and acetoxyisovalerenic acids. This will be easier to do if you remember what an acetoxy group –O–CO–CH₃ is. In the case of acetoxyisovalerenic acid, it is attached to the carbon atom –CH of the isovalerenic acid instead of hydrogen (this carbon atom can be said to be “central” in the molecule of isovalerenic acid, since it is also attached to two –CH₃ groups and one –CH₂).
  Just in case, I remind you once again that, like any carboxylic acids, isovalerenic and acetoxyisovalerenic acids must necessarily contain a –COOH group.
  Isovalerenic acid                            Acetoxyisovalerenic acid