165
10
the Chinese scientist Youyou Tu won the Nobel Prize in 2015. Artemisinin is produced
in the glandular trichomes of Artemisia annua (Asteraceae). Cyt P450 enzymes catalyse
the additional modifications, but the last step, the formation of an unusual peroxide
bridge, is a photooxidation.
The bicyclic valerena-1,10 diene is the starting product for the synthesis of valerenal
and valerenic acid, the latter being the active component in Valerian extracted from
the roots of of Valeriana officinalis (Ricigliano et al. 2016). The bicyclic picrotoxane is
modified into the tricyclic picrotoxin, an equimolar mixture of picrotoxinin and picrotin
(found in the fruit of the Anamirta cocculus, Menispermaceae). Picrotoxin binds GABAgated ion channels. Several other plant-derived sesquiterpenes can cause convulsions
or other symptoms reminiscent of GABA-gated channel blockade. This is the case with
tutin (from Coriaria arborea, Coriariaceae), anisatin (from star anise, Illicium floridanum,
Schisandraceae) and jiadifenolide (from Illicium jiadifengpi, Schisandraceae). Many of
these products contain lactone motifs and show similarity with GABA (. Fig. 8.4). In
New Zealand, honey poisoning with tutin was observed (7 Box 1.1). This was pinpointed
to bees that fed on exudates from an insect that itself had been feeding on Coriaria sp.
bushes (Larsen et al. 2015).
Englerin A (from Phyllanthus engleri, Phyllanthaceae), another compound with a
polycyclic terpene skeleton, is a selective activator of TRPC4 and TRPC5 calcium channels, and this activation of transient receptor potential canonical (TRPC) calcium channels selectively kills renal cancer cells (Carson et al. 2015).
10.6 Sterols and Triterpene (From MVA Pathway, C30)
Two FPP are fused (tail-to-tail) by the squalene synthase to form squalene, which is further oxidized to 2,3-oxidosqualene (Thimmappa et al. 2014; Valitova et al. 2016).
2,3- Oxidosqualene is the precursor for sterols and triterpenes and a substrate for several
oxidosqualene cyclases.
To form sterols 2,3-oxidosqualene is cyclized to lanosterol (in fungi and animals) or
cycloartenol (in plants) via the chair-boat-chair conformation and the protosteryl cation (. Fig. 10.6). Lanosterol gives rise to cholesterol, whereas cycloartenol gives rise to
phytosterols such as β-sitosterol, stigmasterol and the plant hormone brassinosteroid.
Because this backbone is very similar to cholesterol, these compounds can displace lowdensity lipoprotein (LDL) cholesterol in the human intestine. In some plants, cholesterol
formation is also possible, starting from cycloartenol, which is converted into cycloartanol
and further into cholesterol. Additionally, in Solanaceae and Euphorbia lanosterol was
detected, which might contribute to cholesterol biosynthesis. Cholesterol is also a precursor for steroidal alkaloids (see 7 Sect. 12.11 in 7 Chap. 12).
Stigmasterol is present in many plant fats, which are enriched in various vegetables such as seeds (e.g. rape seeds), soy bean and nuts. Stigmasterol is also present in milk. Pasteurization inactivates stigmasterol, a fact that led to its discovery as
the Wulzen factor (antistiffness factor). It had been suggested that stigmasterol could
lessen symptoms of arthritis, and this would have asked for avoiding pasteurized milk.
Stigmasterol can be used as a precursor in the manufacture of semisynthetic progesterone and vitamin D3.
β-Sitosterol is found in vegetable oil, nuts and avocados. Another derivative of
2,3- oxidosqualene is cucurbitadienol and further cucurbitacins from pumpkin, squash or
10.6 · Sterols and Triterpene (From MVA Pathway, C30)
10
the Chinese scientist Youyou Tu won the Nobel Prize in 2015. Artemisinin is produced
in the glandular trichomes of Artemisia annua (Asteraceae). Cyt P450 enzymes catalyse
the additional modifications, but the last step, the formation of an unusual peroxide
bridge, is a photooxidation.
The bicyclic valerena-1,10 diene is the starting product for the synthesis of valerenal
and valerenic acid, the latter being the active component in Valerian extracted from
the roots of of Valeriana officinalis (Ricigliano et al. 2016). The bicyclic picrotoxane is
modified into the tricyclic picrotoxin, an equimolar mixture of picrotoxinin and picrotin
(found in the fruit of the Anamirta cocculus, Menispermaceae). Picrotoxin binds GABAgated ion channels. Several other plant-derived sesquiterpenes can cause convulsions
or other symptoms reminiscent of GABA-gated channel blockade. This is the case with
tutin (from Coriaria arborea, Coriariaceae), anisatin (from star anise, Illicium floridanum,
Schisandraceae) and jiadifenolide (from Illicium jiadifengpi, Schisandraceae). Many of
these products contain lactone motifs and show similarity with GABA (. Fig. 8.4). In
New Zealand, honey poisoning with tutin was observed (7 Box 1.1). This was pinpointed
to bees that fed on exudates from an insect that itself had been feeding on Coriaria sp.
bushes (Larsen et al. 2015).
Englerin A (from Phyllanthus engleri, Phyllanthaceae), another compound with a
polycyclic terpene skeleton, is a selective activator of TRPC4 and TRPC5 calcium channels, and this activation of transient receptor potential canonical (TRPC) calcium channels selectively kills renal cancer cells (Carson et al. 2015).
10.6 Sterols and Triterpene (From MVA Pathway, C30)
Two FPP are fused (tail-to-tail) by the squalene synthase to form squalene, which is further oxidized to 2,3-oxidosqualene (Thimmappa et al. 2014; Valitova et al. 2016).
2,3- Oxidosqualene is the precursor for sterols and triterpenes and a substrate for several
oxidosqualene cyclases.
To form sterols 2,3-oxidosqualene is cyclized to lanosterol (in fungi and animals) or
cycloartenol (in plants) via the chair-boat-chair conformation and the protosteryl cation (. Fig. 10.6). Lanosterol gives rise to cholesterol, whereas cycloartenol gives rise to
phytosterols such as β-sitosterol, stigmasterol and the plant hormone brassinosteroid.
Because this backbone is very similar to cholesterol, these compounds can displace lowdensity lipoprotein (LDL) cholesterol in the human intestine. In some plants, cholesterol
formation is also possible, starting from cycloartenol, which is converted into cycloartanol
and further into cholesterol. Additionally, in Solanaceae and Euphorbia lanosterol was
detected, which might contribute to cholesterol biosynthesis. Cholesterol is also a precursor for steroidal alkaloids (see 7 Sect. 12.11 in 7 Chap. 12).
Stigmasterol is present in many plant fats, which are enriched in various vegetables such as seeds (e.g. rape seeds), soy bean and nuts. Stigmasterol is also present in milk. Pasteurization inactivates stigmasterol, a fact that led to its discovery as
the Wulzen factor (antistiffness factor). It had been suggested that stigmasterol could
lessen symptoms of arthritis, and this would have asked for avoiding pasteurized milk.
Stigmasterol can be used as a precursor in the manufacture of semisynthetic progesterone and vitamin D3.
β-Sitosterol is found in vegetable oil, nuts and avocados. Another derivative of
2,3- oxidosqualene is cucurbitadienol and further cucurbitacins from pumpkin, squash or
10.6 · Sterols and Triterpene (From MVA Pathway, C30)