## 2 Triterpenoids
### 8,9-ene-triterpenoids
Most interestingly, some of the species of _Ganoderma_ can produce pairs of oxygenated triterpenoids that are C-3 \(\alpha\)- or \(\beta\)-relative configuration triterpenoids, and C-3 or C-15 positional isomers such as compounds **256/257** and **264/265**[244]. Although the biogenesis of triterpenoids is obvious, it is interesting to know the biosynthetic pathway along which paired C-3 \(\alpha/\beta\) stereoisomers and C-3/C-15 positional isomers are produced [244]. Further experiments also verified the transformation of 3\(\beta\) into 3\(\alpha\) of triterpenoid when adding the labelled 3\(\beta\) triterpenoid into the liquid culture and 3\(\alpha\) was derived from 3\(\beta\) series through an oxidation-reduction pathway. Multiple pairs of 3\(\alpha\) stereoisomers are produced in cultured mycelia during the production period of the 3\(\beta\) triterpenoids. The corresponding 3-keto metabolite can also be identified in the mycelia [244]. Except for the OH-3\(\alpha/\beta\) stereoisomers, ganoderic acid S\({}_{2}\) (**275**) isolated from a lipophilic extract of the fruiting body of G. _Iuclatum_ is a geometric \(Z\)-isomer of tyromycic acid from _Tryomyces fissilis_[245; 246]. This was confirmed by the NOESY cross peak of H-24/H\({}_{3}\)-27. However, their chemical shifts of C-24, C-25, C-26 and C-27 in the CDCl\({}_{3}\) were the same. Li et al. [246] named compound **275** \"ganoderic acid S\"; nevertheless, the structure of ganoderic acid S should be compound **273**, which was first isolated from _G. lucidum_ by Hirotani et al. [247]. Ganodermanontriol (**291**) was a highly oxygenated lanostane-type triterpenoid and first isolated from _G. lucidum_[248]. Previous studies observed that ganodermanontriol (**291**) showed various biological activities, such as anti-HIV-1, anti-HIV protease and anti-complement [248]. Thus, Kennedy et al. [249] first obtained **291** and its stereoisomeric triols using semi-synthesis from lanosterol (a) over nine steps via the construction of the dieno core and elaboration (part 1) of the 7,9(11)-diene core to triols (part 2). The key steps leading to this family of isomers involved the reconstruction of the trisubstituted alkene using  
Figure 8: 7(8),9(11)-diene-triterpenoids: compounds **64**, **65** decomposed to compounds **261**, **262** in the acid condition. stereoselective and chemoselective phosphonate reactions and the formation of the unusual \(\Delta^{7,9(11)}\)-diene core using the mild acidic opening of a lanosterone-derived epoxide (Figure 9). Ganodermanontriol exhibited significant results on the inhibition and proliferation of breast cancer cells with inhibitory activity (IC\({}_{50}\) = 5.8 uM at 72 h) on the proliferation of MCF-7 cancer cells and IC\({}_{50}\) value of 9.7 uM for the MDA-MB-231 cell line [249]. Figure 9: 7(8),9(11)-diene-triterpenoids: semi-synthesis of ganodermantriol (**291**) and its stereoisomeric triols. Ganodercochlearin C (**293**), ganodecochlearins A and B (**294** and **295**), and 3\(\beta\),225-dihydroxylanosta-7,9(11),24-triene (**297**) were isolated from the fruiting bodies of _G. cochlear_[57]. Compound **296** was an acetyl derivative of **295**. Among them, ganodecochlearins A and B (**294** and **295**) possessed a five-membered ether ring in the side chain and were first identified from _Ganoderma_[250]. However, their analogues, inonotsuoxides A and B with 22,25-epoxyanost-8-ene-3\(\beta\),24S-diol skeleton, were isolated from the scleroota of _Inonotus obliquus_[250]. A group of polyoxygenated lanostanoid triterpenoids, applanoxidic acids A (**298**), B (**299**), C (**302**), D (**303**), E (**300**), F (**301**), G (**304**) and H (**305**) were isolated from two Indonesian tropical macrofungi, _G. applanatum_ and _G. annulare_. The structural characteristics of these compounds were the presence of 7,8-epoxy group, hydroxyl or carbonyl groups at C-12, as well as a hydroxyl group or double bond at C-20.