## 2 The Chemistry of Hemp  
The phytochemistry of industrial _Cannabis sativa_ L. is very complex with more than 500 secondary metabolites isolated and identified, of which a considerable number belongs to the phytocannabinoid class [25]. Phytocannabinoids are terpenophenolic compounds, whose carbon structure is mainly constituted by 22 or 21 carbon atoms, likely an alkyl rescorcinol linking a monoterpene moiety (Figure 1). The polyketide pathway leads to an alkylrescorcinol following the reaction between hexanoyl-CoA with three molecules of malonyl-CoA to yield olivetolic acid (OA). This latter undergoes prenylation by geranyl diphosphate (GPP), that derive from the deoxyxylulose phosphate/methylerythnitol phosphate (DOXP/MEP) pathway [26]. Thus, through the cannabinoid acid synthase (CBGAS) enzyme, mainly expressed in the glandular trichomes of female flowers, cannabigerolic acid (CBGA) is biosynthetized; this last is considered the precursor of all the phytocannabinoids [6; 26]. Subsequently, CBGA is converted into CBDA, CBCA, and \(\Delta^{9}\)-THCA, through the action of flavinylated oxidases, namely cannabididic acid synthase (CBDAS), cannabichromeic acid synthase (CBCAS), and \(\Delta^{9}\)-tetrahydrocannabinolic acid synthase (\(\Delta^{9}\)-THCA) [27]. Indeed, the versatility of phytocannabinoid biosynthesis augments the compounds' structure variability, which further is affected by UV-light and temperature. Thus, phytocannabinoids differ into ten different main types (e.g., CBD-, \(\Delta^{9}/\Delta^{8}\)-THC-, CBG-, CBN-, CBND, CBT-, CBL-, CBE-, or CBC-type (Figure 2). A \"miscellaneous\" type is also reported, to which some different molecules, not chemically complying with the most common phytocannabinoids, such as cannabifuran (CBF-C5), dehydrocomanabifuran (DCBF-C5), cannabicoumaronone-C5 (CBCON-C5).  
Figure 1: (**A**) General overview of cannabinoids’ biosynthetic pathway; (**B**) Butanoyl-CoA is involved in the biosynthesis of propyl cannabinoids, of which cannabigerovarinic acid (CBGVA) is the precursor compound.  
Acetyl-CoA and butanoyl-CoA also react with malonyl-CoA derived-polyketide to produce other cannabinoid derivatives. In this context, a well-known example is cannabidi-varinic acid, which could be considered a CBDA propyl analogue [7]. Moreover, acidic phytocannabinoids could undergo nonenzymatic decarboxylation to yield the neutral forms, which often retain or enhance the bioactivity of their precursors.  
Beyond phytocannabinoids, _Cannabis sativa_ L. is a source of a plethora of other compounds with pharmacological potential [28] such as terpenoids, alkaloids, and polyphenols (e.g., flavonoids, sttilbenes, phenylpropanol amides, lignanamides) [29]. In hemp, different flavonoids, that have been identified from pollen, leaves, and flowers, have as aglycone quercetin, kaempfer, orientin, apigenin, and luteolin [30]; these flavonoids could be present as C- or O-glycos conjugates. Methylated preynlated flavones, cannflavins A, B, and C, as well as flavonoids glycerosides, such as kaempfer 3-O-sophorooside and quercetin 3-O-sophorooside, were also isolated from hemp pollen [31]. Furthermore, from _Cannabis sativa_ L. fruits, beyond to a source to produce an oil rich in tocopherols and mono-, di-, and polyunsaturated fatty acids (PUFA) such as \(\alpha\)-linolenic (ALA), \(\gamma\)-linolenic acid (GLA), and stearidonic acid (SDA), contained different phenylamides, tyramine and octopamine derivatives of hydroxycinnamic acids, and their lignanamides, also called cannabis [32; 33].