How to remember saponin formulas

Rule number four:
Live in the world with science.

How to remember saponin formulas?

Saponins are another rather difficult subject to grasp.
First, it’s important to understand that saponins are divided into triterpene and steroid types.
Second, all saponins are glycosides. The aglycone portion of saponins is called sapogenin. The sugar portion of saponins is most often glucose, galactose, xylose, or rhamnose.
You should start by memorizing the basic skeleton of the cyclopentanoperhydrophenanthrene formula (4 rings, 3 of which are six-membered and one is five-membered) and the numbering of its carbon atoms (usually this doesn’t cause much difficulty).

    Cyclopentaneperhydrophenanthrene

  A number of saponins are its derivatives. We’ll draw the cyclopentane ring with the triangular protrusion facing upward and draw “lines” at the positions С₁₀, С₁₃ and С₁₄. These “lines” denote in our country (yes, and not only in our country, but very often in scientific chemical literature as well) a group СН₃, which chemists agreed not to indicate in cases of complex molecules, so as not to clutter the drawing. So, the group itself СН₃ It’s not necessary to label it, but a single bond must be drawn to it (as you can see in the figures of all saponin formulas).
Now let’s move on to the formulas themselves.
General rule: absolutely all triterpene saponins contain “antennae” in the position С₄ (that is, two –СН₃ groups).
  Triterpene saponins are tetracyclic and pentacyclic.

Tetracyclic triterpene saponins have four closed conjugated rings.

To the cyclopentanoperhydrophenanthrene skeleton with additions (+ dash in С₁₀, С₁₃ and С₁₄ + “whiskers” in С₄) At the top of the triangular protrusion of the cyclopentane ring, we draw a “double fence with protrusions”, as some students call it. This yields the formula for lanostane.

  Lanostane

  We connect the line that comes out of the position with a triangle С₁₀, with the position С₉ (that is, we get another small cyclic ring – cyclopropane). Everything else remains as in lanostane. This compound is called cycloartane. Cycloartane derivatives are found in milkvetch.

  Cycloartane

  If in the formula of lanostane the dash from the position С₁₃ move to С₈ (inside the cyclohexane ring), we obtain the formula of dammarane. This formula is very important because saponins—dammarane derivatives—are found in ginseng, and they are the ones that exert its adaptogenic effect.

  Dammarane

  Remember the location of the dashes in the dammaran formula (С₁₀, С₈, С₁₄), Because these bonds will remain in all the formulas of triterpene saponins, which you need to know.

Pentacyclic triterpene saponins have five closed conjugated rings.

The formula of lupane contains four cyclohexane rings and one cyclopentane ring. At the junction between them (rings D–E, the position С₁₇) draw a line (remember also about the “antennae” in С₄, dashes in С₁₀, С₈, С₁₄). That is, we currently have 6 lines that will be characteristic of all pentacyclic triterpene saponins.

  Lupane

   Lupane differs from other pentacyclic triterpene saponins in that:
1) the presence of a cyclopentane ring (in all others, the fifth cyclic ring is cyclohexane);
2) the Mercedes emblem (only without the circle), emerging from the corner of the cyclopentane ring E (position С₁₉).
  Triterpene saponins—lupane derivatives—are characteristic of yellow lupine, mistletoe, and sticky alder.

The other pentacyclic triterpene saponins you need to know are derivatives of ursane or oleanane. Their molecules consist of five cyclohexane rings and have all six bars discussed above (see lupane).
Ursane was the first saponin to be isolated; it was obtained from bearberry (Arctostaphylos uva-ursi, hence the name). Alpha-amyrin is based on it. To remember this, remember that the first identified saponin was ursane; alpha is the first letter of the Latin alphabet; therefore, ursane is logically related to alpha-amyrin.

  Ursane                                                           alpha-Amyrin

  The second pentacyclic saponin, whose derivatives are also called amyrins, is oleanane, which was isolated from the olive tree Olea europaea, hence its name. Beta-amyrin is based on it.

Oleanane                                                 beta-Amyrin

  Ursane and oleanane derivatives make up the bulk of triterpene saponins found in plants.
Now, let’s look at their structure. They differ from each other by the presence or absence of –СН₃ groups in ring E in positions С₁₉ and С₂₀. So, ursane has one –СН₃ group both in С₁₉ and in С₂₀ (two parallel lines in the picture), and oleanane has two –СН₃ groups in С₂₀ (“antennae”).
    Accordingly, alpha-amyrin also has two parallel lines, and beta-amyrin has “antennae”.
We’ve already memorized the alpha and beta positions in linalool molecules (remember the acyclic monoterpenoids—the components of essential oils?). Let’s review: alpha is the first letter of the Latin alphabet; parallel lines do not intersect—the first thought (our parallel lines in alpha-amyrin and ursane); beta is the second letter; the possibility of parallel lines intersecting (these are the “antennae” in beta-amyrin and oleanane)—the second thought.
Thus, ursane and oleanane molecules have 5 cyclohexane rings and 8 –СН₃ groups (lines).
  Alpha- and beta-amyrins are based on ursane and oleanane, respectively. Their structure also contains –ОН group in position С₃ (it is to this that sugar residues are most often attached) and a double bond in the C ring between С₁₂ and С₁₃ atoms.
  Their derivatives are ursolic and oleanolic acids (which, by the way, often cause the acidic reaction of saponin foam, which distinguishes it from soap foam, which has an alkaline reaction). The molecules of these acids are formed by the addition –СООН group in position С₁₇ instead of a group –СН₃.
  Another well-known acid—a derivative of oleanane and beta-amyrin—is glycyrrhetinic acid, which is found in licorice roots. Its structure is similar to beta-amyrin, but it differs from it by the presence of a quinoid group (С=О) in position С₁₁ and replacing one of –СН₃ groups of “antennae” (namely, groups in position С₃₀) to the acid group –СООН.
  It is the presence of the С=О group in position С₁₁ determines the hormone-like properties of glycyrrhetinic acid and licorice root (corticosteroids contain a similar group, see below, for example, cortisone).

  Glycyrrhetinic acid

  In general, ursane derivatives are less common in the plant kingdom than oleanane derivatives. The former are found in Orthosiphon stamineus and have a diuretic effect, while the latter, as already noted, are found in licorice, as well as calendula, horse chestnut, polemonium, and aralia, and are responsible for anti-inflammatory, antispasmodic, expectorant, venotonic, capillary strengthening, and tonic properties.

Steroidal saponins also have the formula cyclopentanoperhydrophenanthrene. They are often used to synthesize steroid hormones, particularly cortisone, the formula of which you should know.

  Cortisone

  Unlike triterpene saponins, steroids and steroidal saponins do not have –СН₃ groups (lines) directed downwards, but they are directed only upwards. Thus, cortisone contains 2 such groups – in positions С₁₀ and С₁₃. In addition, it has two more quinoid groups (С=О) in the cyclohexane rings themselves in positions С₃ and С₁₁, and another one – in the branched “antennae” that extends from С₁₇ (where the “fence” is located in tetracyclic triterpene saponins). As you probably guessed, if we are talking about one “antenna”, then there must be a second one, which also extends from С₁₇, but it ends not with –СН₃ group, but with a group –ОН. By the way, the branched “antennae” also ends –ОН a group, but not an independent one, but as part of a group –СН₂ОН.

  Regarding monodesmosides and bidesmosides, which represent the structure of steroid saponins, they contain 3 –СН₃ groups (dashes) directed upwards – in positions С₁₀, С₁₃ and С₁₈. This last bond is located in a new heterocyclic ring, absent from all the other compounds we have considered so far – the 5-membered lactone ring E. However, the structure of monodesmosides is not limited to the lactone ring alone. They have another lactone ring – a 6-membered one (ring F), which seems to lie on its side and with its “nose” touches the upper right corner of the 5-membered heterocyclic ring, and on the opposite side has a “tail” (that is, again –СН₃ group).
 In addition, both mono- and bidesmosides have an –OH group at position С₃, to which sugar residues readily attach (as is also characteristic of cardiosteroids and triterpene saponins), and a double bond between atoms С₅ and С₆ of cyclohexane ring B.

  Diosgenin

  Thus, we have described the structure of the main monodesmoside, diosgenin. It is found in the rhizomes of Dioscorea nipponica and other Dioscorea species, which is where the first part of the name “diosgenin” comes from. The second part indicates the aglycone nature of the compound.
Diosgenin is the basis for its glycoside, dioscin, which contains three sugar residues at position С₃: one glucose molecule, to which two rhamnose molecules are attached.

  Dioscin

  In bidesmosides, the 6-membered heterocyclic ring opens with the corresponding formation of aglycone or glycosides, in which sugar residues are not added in С₃ position, as in monodesmosides, but on an open ring instead of a hydrogen atom in the –OH group.

  Bidesmoside (R=H or Glu)

  Steroidal saponins, found in Dioscorea, Tribulus terrestris, and fenugreek, have an anti-cholesterolemic effect and serve as a raw material for the production of corticosteroids.

If you’ve successfully mastered this challenging material, congratulations! You’ve taken the second significant step toward mastering pharmacognosy. Now you know some things, including complex material. But much more lies ahead. Don’t relax!