## 2 The Phytochemistry of _Artemisia annua_ L. (Qinghao)
### Sesquiterpenenoids
#### 2.6.4 Tricyclic Sesquiterpenes  
Several tricyclic sesquiterpenes are known from _A. annua_, although none have been reported in very significant quantities. These include _a_-longipinene (**522**) (3-longipinene [5989-08-2]) [22,66], _b_-longipinene (**523**) ([41432-70-6]) [27] and _trans_-longipinocarveol (**524**) ([889109-69-7]) [23], which are representatives of the longipinane (2,6,6,9-tetramethyltricyclo[5.4.4.0 2,8]undecane, 9 CI) skeleton. Longifolene (junipene [475-20-7]) (**525**) [28] is a longifolane sesquiterpenoid (decahydro-4,8,8,9-tetramethyl-1,4-methanoazoline, 9 CI).  
The acorane (1,8-dimethyl-4-(1-methylethyl)spiro[4.5]decane, 9 CI) and chamigrane (11,5,9-tetramethylspiro[5,5]undecane, 9 CI) sesquiterpenoids: _b_-acorenol (3-acoren-11-ol [28400-11-5]) (**526**) [19] and _b_-chamigrene (2,7(14)-chamigradiene [18431-82-8]) (**527**) [19] are also included here.  
The largest group of tricyclic sesquiterpenes to be described rom _A. annua_ is the cedranes (Table 41). A cDNA clone encoding _epi_-cedrol synthase has been shown to catalyze the formation of the oxygenated sesquiterpene _epi_-cedrol from FPP (**378**) [258,259]. Trace amounts of the sesquiterpene hydrocarbons _a_-cedrene, _b_-cedrene, _e_-)-_g_-f_-f_-f_-senesene, _a_-acoradiene and (_E_-)-_b_-bisabolene were also produced by the operation of this enzyme [258]. The structure of 3\(a\),15-dihydroxycedrane (**534**) from _A. annua_ has been rigorously determined both by 2D-NMR and by synthesis from (+)-_b_-cedrene [9].  
Other tricyclic sesquiterpenes from _A. annuua_ belong to the silphinane (decahydro-1,4,4,5a-tetra-methylcyclopenta[c]-pentalene); isocomane (dehydro-1,3a,4,5-tetramethylcyclopenta[c]pentalene); \(\alpha\)-santalane (2,3-dimethyl-2-(4-methyl-pentyl)tricycle[2.2.1.0\({}^{2,6}\)]-heptane); copaane (1,3-dimethyl-8-(1-methylyl)tricyclo[4.4.4.4\({}^{2,7}\)]decane, 9 CI); bourbonane (decahydro-3a,6-dimethyl-1-(1-methylyl))-cyclobuta[1,3:3,4]-dicyclopentene, 9 CI); and \(\alpha\)-_trans_-bergamotol classes of sesquiterpenoid. These include: silphinene (1-silphinene [74284-57-4]) **(535)**[27], \(\alpha\)-isocompene (isocompene [65372-78-3]) **(536)**[27], \(\beta\)-isocompene (3(13)-isocompene [74311-15-2]) **(537)**[27], (\(Z\))-\(\alpha\)-santalol (\(\alpha\)-santal-10-en-12-ol [115-71-9]) **(538)**[19], \(\alpha\)-copaene(3-copaene [3856-25-5]) **(539)**[19, 22-24, 31, 43, 45, 48, 50, 66], \(\beta\)-copaen-4\(\alpha\)-ol (tricyclol[4.4.0.0\({}^{2,7}\)]decan-4-ol, 1-methyl-3-methylene-8-(1-methylyl)-, (1\(R\),2\(R\),4\(S\),6\(S\),7\(S\),8_)- [124753-76-0]) **(540)**[43], \(\alpha\)-ylangene ([14912-44-8]) **(541)**[25,30,40,113], \(\beta\)-bourbonene (4(15)-bourbonene [5208-59-3]) **(542)**[45], \(\alpha\)-bergamotol [88034-74-6]) **(543)**[27, 32, 43], _trans_-\(\alpha\)-bergamotyl acetate ([87978-33-4]) **(544)**[27, 43], _trans_-\(\alpha\)-bergamotyl acetic anhydride ([960148-87-2]) **(545)**[32], \(\alpha\)-neoclovene ([4545-68-0]) **(546)**[41,50], (-)-neoclovene-(II) [56684-96-9] **(547)**[46], neoisolongifolene [79982-57-3] **(548)**[48] and 4,4,8-trimethyltricyclol[6.3.1.0\({}^{(1,5)}\)]-dodecane-2,9-diol ([372968-04-2]) **(549)**[20].