## 2 The Phytochemistry of _Artemisia annua_ L. (Qinghao)
### Monoterpenoids  
Monoterpenoids generally contain ten carbons (C\({}_{10}\)) and are the principal components of the essential oil of _A. annua_ obtained by steam distillation (or other techniques that are selective for more volatile natural products). It is widely believed that monoterpenes are located in the glandular trichomes - small structures, which are loosely attached to the surfaces of the leaves and flowers [108].  
\begin{table}
\begin{tabular}{|l|l|l|l|} \hline
**Name** & **Alternative Name(s)** & **CAS Number** & **References** \\ \hline _4H_-1-Benzopyran-4-one 5-hydroxy-2–(2-hydroxy-3,4-di-methoxyphenyl)-3.7-dimethoxy **(235)** & & [1186306-45-5] & [15] \\ \hline _4H_-1-Benzopyran-4-one, 2-(3,5-dihydroxy-4-methoxy-phenyl)-3-(\(\beta\)-D-glucopyranosyloxy)-5,7-dihydroxy- **(236)** & & [230283-37-1] & [71] \\ \hline Mearnsetin **(237)** & 3,3’,5,5’,7-Pentahydroxy-4’-methoxy-flavone & [16805-10-0] & [71] \\  & 2-(3,5-Dihydroxyphenyl-4-methoxy-phenol)-3,5,7-trihydroxy-4H-1-benzopyran-4-one & & \\  & 3’,5’,5’,7,7-Tetrahydroxy-4’-methoxy-flavonol & & \\ \hline Chrysosplenol E **(238)** & 2’,3,4’,5,5’,7-Hexahydroxyflavone & [23289-81-8] & [80] \\  & 3,4’,5’,7’-tetramethyl ether & & \\  & 2’,5-Dihydroxy-3,4’,5’,7-tetramethyl-flavone & & \\  & & flavone & \\ \hline
5,3’-Dihydroxy, 3,6,7,5’-tetramethyl flavone **(239)** & & [99] \\ \hline
3’,5,7,8-Tetrahydroxy-3,4’-dimethoxyflavone **(240)** & 3,3’,4’,5,7,8-Hexahydroxyflavone 3,4’-di-ethyl ether & [123563-74-6] & [76, 94] \\ \hline \end{tabular}
\end{table}
Table 22: Other Hexahydroxy Flavonols.  
The regular acyclic monoterepenes which are described in Section 2.5.1 consist of an eight-carbon chain, which is often functionalized at the 1-position, with methyl substituents at the 3- and 7-positions (Table 23). They are formed by ionization of the pyrophosphate group in one of the C\({}_{10}\) precursors: geranyl pyrophosphate (GPP), nervl pyrophosphate (NPP) or linalyl pyrophosphate (LPP) (Figure 2) [these monoterepene precursors are, in turn, formed from the \"head-to-tail\" condensation of a \"starter\" molecule of dimethylhyprophosphate (DMAPP) with a \"chain extender\" of isopentenyl pyrophosphate (IPP) (both C\({}_{5}\))]. _A. annua_ is also a rich source of irregular acyclic monoterepenoids (Section 2.5.2), which are derived from the \"head-to-middle\" condensation of two C\({}_{5}\) precursors.  
The \"regular\" acyclic monoterepenoid precursors can then undergo further intramolecular reactions to yield monocyclic monoterepenes (Section 2.5.3). The largest group of such monocyclic monoterepenes in _A. annua_ is the \(p\)-menthane series (Table 25), which incorporate a single six-membered ring. Further cyclization produces bicyclic monoterepenes (Section 2.5.4), which may contain an additional five-membered ring (e.g., camphanes in Table 26); or a four-membered ring (pinanes, Table 27); or a three-membered ring (thujanes, Table 28). Studies with \({}^{14}\)C-labeled LPP have shown that in _A. annua_ this precursor is converted to cyclised monoterepenes such as 1,8-cineole (**326**) and \(\alpha\)-pinene (**347**) with greater efficiency than the alternative precusors, NPP and GPP [109].