## 2 The Phytochemistry of _Artemisia annua_ L. (Qinghao)
### Sesquiterpenenoids
#### 2.6.3.2. Cadinanes, Muurolanes and Amorphanes  
The amorphane/cadinane group of bicyclic sesquiterpenes is by far the largest class of sesquiterpenes found in _A. annua_. Unfortunately, the nomenclature and stereochemistry reported for cadmiumes and amorphanes in the literature has sometimes become quite confusing. In this review, the relative stereochemistry at the 1-, 6- and 7-positions is used to define four skeletal types, according to guidelines which are set out in the Dictionary of Natural Products [16]. Thus, in the cadinane skeleton, the decalin ring is _trans_-fused (1\(\alpha\),6\(\beta\),7\(\beta\)), while in the muurolane skeleton (1\(\beta\),6\(\beta\),7\(\beta\)), it is _cis_-fused. The cadinane and muurolane sesquiterpenes found in _A. annua_ have been grouped together in Table 35. Amorphane sesquiterpenes also incorporate a _cis_-decalin ring junction, but differ from the muurolane sesquiterpenes in their relative stereochemistry at the 7-position. The very large group of amorphane sesquiterpenes from _A. annua_ is listed in Table 36. (No representative of the bulgarane sesquiterpenes (1\(\alpha\),6\(\beta\),7\(\alpha\)), the fourth possible skeleton allowed by this classification scheme, is known from _A. annua_). \begin{table}
\begin{tabular}{|l|l|l|l|} \hline
**Name** & **Alternative Name(s)** & **CAS number** & **References** \\ \hline _Cadinanes_ & & & \\ \hline Artemisinol (**433**) & 12-Cadinanol & [82890-78-6] & [143] \\ \hline \(\delta\)-Cadinene (**434**) & 1(10),4-Cadinadiene & [483-76-1] & [19, 23, 30, 31, 32, 40, 43, 48, 51] \\ \hline
14-Hydroxy-\(\delta\)-cadinene (**435**) & & [153408-92-5] & [27] \\ \hline
4(15),5,11-Cadinatriene (**436**) & 1-_epi_-Bicyclosesquiphellandrene_ & [54274-73-6] & [48] \\ \hline \(\alpha\)-Cadinene (**437**) & 4,9-Cadinadiene & [24406-05-1] & [111, 130] \\ \hline \(\beta\)-Cadinene (**438**) & 3,9-Cadinadiene & [523-47-7] & [22, 66] \\ \hline \(\gamma\)-Cadinene (**439**) & 4(10),15-Cadinadiene & [39029-41-9] & [32, 34, 40, 43] \\ \hline \(\alpha\)-Cadinol (**440**) & 4-Cadinen-10-ol & [481-34-5] & [19, 43, 45] \\ \hline \(\gamma\)-Cadinol (**441**) & 2-Naphthaleneol, 1,2,3,4,4a,7,8,8a-octahydro-2,5- & [50895-55-1] & [45] \\  & dimethyl-8-(1-methylethyl)- & & \\ \hline _cis_-Calamene (**442**) & & [72937-55-4] & [32, 43] \\ \hline Cubenol (**443**) & 4-Cadinen-1-ol & [21284-22-0] & [19, 43] \\ \hline _epi_-Cubenol (**444**) & 4-Muurolen-1-ol & [19912-67-5] & [41] \\ \hline _Muurolanes_ & & & \\ \hline \(\gamma\)-Muurolene (**445**) & 4,10(14)-Muuroladiene & [30021-74-0] & [43] \\ \hline \(\delta\)-Muurolene (**446**) & 4(15),10(14)-Muuroladiene & [1136-29-4] & [23] \\ \hline
4-Muurolen-10-ol (**447**) & Cedrelanol & [5937-11-1] & [25] \\ \hline \(t\)-Muurolol (**448**) & 4-Muurolen-10-ol (1\(\beta\), 6\(\beta\), 7\(\beta\),10\(\beta\)) & [19912-62-0] & [19] \\ \hline \end{tabular}
\end{table} 
Table 35: Cadinane and Muurolane sesquiterpenoids (Decahydro-1,6-dimethyl-4-(1-methylethyl))-naphthalene, 9 CI). Both the synthesis [144] and NMR properties [145,146] of amorphane and cadinane sesquiterpenes from _A. annua_ have been reviewed. Artemisinic acid (**473**) [105,147,148], arteannuin B (**462**) [105,147,149] and artemisinin (**495**) [105,147,150] are the most abundant representatives of this class of natural products and were amongst the first sesquiterpenes to be reported from _A. annua_. Several of the amorphane sesquiterpenes in Table 36 have since been implicated as biosynthetic precursors to artemisinin (**495**), which has been classified as a _seco_-cadinane in Table 37 (the prefix \"_seco_-\" indicates that carbon-carbon bond cleavage has occurred - in this case between C-4 and C-5). The amorphane sesquiterpene, artemisininic acid (**473**) (Table 36) was first isolated in 1981 by Prof Tu's group [151]. Its structure was confirmed both by X-ray crystallography [148, 152] and by NMR spectroscopy [153]; and subsequently by synthesis [154, 155]. Depending on the chemotype of _A.