## 5 De Novo Synthesis of EGCG and Methods of Isolation  
Total and enantioselective synthesis of epigallocatechin 3-O-gallate was carried out in 2000 by [PERSON] and [PERSON] with an overall 19% yield [64]. The key step in this synthesis route was a stereospecific cyclization of the Sharpless asymmetric dihydroxylation intermediate. Substrates were simple aromatic compounds with hydroxyl groups protected with benzyl moieties (Scheme 1). The synthetic pathway consists of 8-9 steps and at some points involves low-temperature conditions (\(-\)78 \({}^{\circ}\)C). To sum up, the synthetic procedure is complex and lengthy. Therefore, many methods of EGCG extraction from raw plant materials have been applied and become more popular than chemical synthesis approaches. Isolation of EGCG is also not an easy process due to the presence of many structurally related compounds in the extract [65]. Methods used to isolate biomolecules from tea extract, which have been presented in the literature concern the following approaches: conventional solvent extraction technique, ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), high-pressure processing (HPP), supercritical fluid extraction (SFE), and subcritical water extraction (SWE) [66]. When performing isolation of catechins from tea, one should remember to plan the decaffeination step during the process. Separation of tea polyphenols is performed by membrane separation (ultrafiltration), supercritical fluid extraction (SFE) with carbon dioxide, precipitation, as well as adsorption on polymers (resins) [18]. These methods differ in many aspects. Some of them are better in terms of cost-effectiveness, some others are recognized as green chemistry. The analysis provided by Monsanto shows that the most promising method for isolation of polyphenols from green tea is precipitation, whereas for black tea, adsorption methods are recommended [18]. Interactions of green tea extracts and EGCG with various active pharmaceutical ingredients were noted in various areas, namely at biopharmaceutical level, as well as pharmacokinetics and pharmacodynamics. Taking into account biopharmaceutical level, very interesting interactions of green tea extracts, EGCG and components of their formulations were observed with selected APIs. An interesting preliminary study on this subject was performed by [PERSON] et al. with the use of beverages containing green tea extract and cyclodext [67]. They observed interactions of various P-glycoprotein substrates such as digoxin with cyclodext that can significantly increase the solubility of this API leading to its overdose and to subsequent toxic effects. Therefore, the authors concluded that cyclodextrin-containing foods and beverages, which also contain green tea extracts (GTSs) should be avoided when a patient uses some other low-soluble drugs. Many other interesting interactions of green tea extracts and EGCG and components of their formulations were observed with selected APIs on the pharmacokinetics and pharmacodynamics levels. Various published studies describe the synergistic and additive effect of EGCG and anticancer agents as well as their influence on the inhibition of neoplastic processes both in vitro and in vivo. A significant analysis on the subject was presented by [PERSON] et al. [68]. They offered various possibilities of EGCG leading to an increase in the effectiveness and safety of anticancer treatment. First, it was found that when EGCG is used as a chemosensitizer, doses of many anticancer drugs, including 5-fluorouracilacil, cisplatin, or tamoxifen, can be decreased, thus simultaneously reducing the risk of their side effects. Secondly, both EGCG and its metabolites are thought to modulate tumor cells' response to ionizing radiation. Finally, the EGCG antioxidant and anti-inflammatory activity could reduce the risk of various side effects caused by chemo- and radiotherapy, including intestinal mucosa damage, changes in hematological parameters or nephro- and cardiotoxicity.