Limonoids, Quassinoids, and Related Compounds

Two major groups of metabolically altered triterpenes, the limonoids (tetranortriterpenoids) and the quassinoids (decanortriterpenoids) are derived from the triterpenoid precursor euphol.

These compounds are limited in distribution to the families Rutaceae, Meliaceae, Cneoraceae, Simaroubaceae, and perhaps the Burseraceae.

Biosynthesis of limonoids and quassinoids

These compound presumably arise from mevalonic acid pathways as the triterpenoid precursor euphol is a key intermediate in their biosynthesis.

Both groups of compounds are derived by condensation of a chair-chair-chair-boat configured squalene epoxide precursor. Most of the intermediates and enzymes in these pathways remain unstudied. Euphol appears to be the precursor of most of these compounds, although another compound tirucallol (with opposite configuration at C-20) may be involved in the formation of some compounds.

Δ⁷-euphol and/or Δ⁷-tirucallol appear to be later intermediates in the pathway. apo-Euphol and apo-tirucallol, C₃₀ compounds or protolimonoids, have features that also suggest that they are intermediates.

Limonoids or tetranortriterpenoids

There are at least 300 known members of this group of compounds. They are stereochemically homogeneous. They are found only in the Meliaceae, Rutaceae, Cneoraceae and Harrisonia of the Simaroubaceae.

Oxidative modification results in removal of the four terminal side-chain carbons and formation of a β-substituted furan ring.

Various classes of limonoids have the A, B, C, or D ring (or some combination of them) cleaved. For example, limonin has a cleaved A ring and D ring and is a A,D-seco-limonoid. The initial products of the oxidation process are concealed by secondary cyclization.

Quassinoids or decanortriterpenoids

Quassinoids occur only in the family Simaroubaceae. More than 120 compounds of this type have been described.

The biosynthetic precursors of this series are similar to those of limonoids. Δ⁷-euphol and/or Δ⁷-tirucallol appear to be involved. After a series of reactions, cleavage of the C₁₃-C₁₇-bond leads to the formation of C₂₀-quassinoids.

Inadequate data exist to define clearly the pathway of biosynthesis.

Pentanortriterpenoids

This series of compounds have been isolated from members of the family Cneoraceae. Limonoids also are found in these plants.

Antifeedant properties

Other limonoids from the same plant have feeding deterrent activity. A similar series of compounds is found in a related plant Melia azadirachta. The fruits of this species are quite toxic to livestock.

Medicinal properties.

Many limonoids and quassinoids have antitumor effects. Most, however, have proven too toxic for practical use in cancer therapy.

Certain quassinoids have activity against Plasmodium falciparum, one of the organisms responsible for malaria. In general their toxicity precludes use in humans as antimalarial compounds.

A number of quassinoids have antileukemic acitivity.

Limonin in orange juice

Because juice of oranges is of major economic importance, the development of bitter taste, caused by the formation of limonin from precursors in the juice has been studied. Limonoid synthesis occurs in the leaves and the compound is transported into the fruits under normal conditions. In juice, the precursor a salt of limonoic acid A-ring lactone is converted into limonin. The rate of limonin formation is enhanced by pasteurization. Several approaches have been examined to prevent the formation of bitterness in orange juice.

Bioactive limonoids

apo-Tirucallol and apo-euphol biosynthesis

Turreanthin, melianone, grandifoliolenone and related compounds

Limonin biosynthesis

Assorted limonoids

Biogenesis of quassinoids

Lecture Slides

Plants with Limonoids, Quassinoids, and Related Compounds

© David S. Seigler, Integrative Biology 425, Plant Secondary Metabolism, Department of Plant Biology, 265 Morrill Hall, 505 S. Goodwin Ave., University of Illinois, Urbana, Illinois 61801, USA. 217-333-7577. seigler@life.uiuc.edu.