**2. Results and Discussion**

#### *2.1. Large-Scale Isolation of OOPs*

The property of secoiridoid phenolic aldehydes such as oleocanthal (**1**) that allows them to react with water and generate water-soluble hydrates such as oleocanthadiol (**8**) [66] was used to develop methods of selective extraction without the application of a final chromatographic purification. The avoidance of chromatography is a very important advantage in comparison with the known methods of isolation [30,34–41], permitting the easy and cost-effective scale-up of the isolation procedure.

#### *2.2. Isolation of Oleocanthal (1)*

Oleocanthal (**1**) can be easily extracted from olive oil using water [30,67]. Oleocanthadiol (**8**), the product of oleocanthal's (**1**) reaction with water, is a water-soluble compound while the rest of the olive oil's lipophilic ingredients remain in the oil-containing phase. Evaporation of the aqueous phase as a next step in the procedure provided pure oleocanthal (**1**). It is important to note that successful application of this method requires that the starting material of olive oil does not contain secoiridoid phenolic aldehydes other than oleocanthal (**1**). Screening of thousands of olive oil samples using qNMR [35] led to the identification of an olive fruit variety (i.e., the Kalamon variety), which under appropriate milling conditions gives olive oil containing only oleocanthal (**1**) as secoiridoid phenolic aldehyde [8,68]. Starting with this type of olive oil, the described method provides pure oleocanthal (**1**) in one extraction step. When the starting material is an olive oil containing additional secoiridoid phenolic aldehydes, the water extraction step leads to a mixture of oleocanthal (**1**), oleacein (**2**), oleuropein aglycone (**3a,b**) and ligstroside aglycone (**4a,b**) that can be further purified using classic chromatographic methods, as previously reported [35].
