## 3 DES as Synthesis Media of Natural Based Chemicals  
DESs have been widely used as green synthesis media since early 2000, timidly at first (with just a dozen articles a year), and with much greater intensity a few years later (Figure 3, Web of Science).  
During 2000, DES have been used both as the solvent of the reaction and the source of the template (structure-directing agents); the so called-ionothermal synthesis. This strategy provided opportunities to develop new synthetic routes for the preparation of several organometallic chemicals [96; 97; 98; 99; 100; 101].  
At the early stage of the research, the green character of these compounds is already visible (biodegradability, reuse, low volatility) while unexpected catalytic properties have been found [102; 103]. Quickly, DESs began to be studied as a mean of synthesis in the preparation of many types of chemical substances of a very different nature; inorganic materials such as silicas, metal charlcogenides, metal structures, organosilicas, metal oxides or metal salts [104], polymers [105], micro/nano structures such as microtubes [106], microporous materials [107], nanowires [108], or carbon absorbent [109] among many others [110].  
Focusing on preparation of chemicals with natural bases, DES has been used in the synthesis of biodiesel. Habitually, biodiesel is prepared from animal fats or vegetable oils or biomass such as yeasts, molds, algae, soybean, or pine trees [111]. The traditional processes for preparing biodiesel present several limitations such as emulsification problems, corrosion and energy, waste production, and the saponification of fatty acids, among others. Investigations on the preparation of biodiesel using ionic liquids or DESs by means of enzymatic routes have revealed that less waste is produced and not such severe conditions are needed [111]. Nevertheless, these new processes are still challenging, and some difficulties must still be overcome (the compatibility with non-aqueous solvents, for instance).  
On the other hand, DESs have been widely used for biotransformations such as (trans)esterifications, polymerization of lactone, aminolysis, or epoxidation involving lipase-catalyzed processes such as in [112] or epoxide hydrolase reactions [113].  
Regarding the synthesis of natural products with biological and pharmaceutical applications, DESs have been useful in the preparation of quinazolinones (marketed as drugs due to their anticonvulsant, hypotensive, sedative, antidepressant, anti-inflammatory,  
Figure 3: Manuscripts in which DESs have been used as synthesis media from 2006 to 20 October 2021. Source: Web of Science.  
and anti-allergy properties) mediated cyclization strategy. Results indicated that the new process was cheaper, since the starting material, anthranilamide, is low-priced with respect to the initial raw material and greener, in good to excellent yields [114]. The same strategy was used to synthesize another type of alkaloid, a penipanoid type, with successful results [115].  
Another important feature in the use of DESs for the synthesis of natural products is the facility of reuse and the decrease in the waste produced. For example, [PERSON] et al. synthesized 2H-chromene (structural motif in natural products with important biological activity) via DESs in moderate and good yields, with the advantage of being able to recycle the used DES at least five times [116].  
Finally, another popular strategy is the use of DES as biocompatible building blocks as a reactant, medium, and/or catalyst in the design of green novel synthetic protocols. The reaction of 4-chlorobenzaldehyde, malononitrile, and hydrazine hydrate was studied under two different reaction protocols (one-pot stepwise pattern and adding reactants simultaneously) in the presence of various deep eutectic solvents, without using any extra catalyst. Once again, the DES was reused and recycled four times with little loss of reactivity [117].