Reaction of the Phytochemistry Community to Green Chemistry: Insights Obtained Since 1990

Abstract

This review article aims to study how phytochemists have reacted to green chemistry insights since 1990, the year when the U.S. Environmental Protection Agency launched the “Pollution Prevention Act”. For each year in the period 1990 to 2019, three highly cited phytochemistry papers that provided enough information about the experimental procedures utilized were sampled. The “greenness” of these procedures was assessed, particularly for the use of solvents. The highly hazardous diethyl ether, benzene, and carbon tetrachloride did not appear in the papers sampled after 2010. Advances in terms of sustainability were observed mainly in the extraction stage. Similar progress was not observed in purification procedures, where chloroform, dichloromethane, and hexane regularly have been employed. Since replacing such solvents in purification procedures should be a major goal, potential alternative approaches are discussed. Moreover, some current initiatives toward a more sustainable phytochemical research considering aspects other than only solvents are highlighted. Although some advances have been achieved, it is believed that natural products chemists can play a major role in developing a novel ecological paradigm in chemistry. To contribute to this objective, six principles for performing natural products chemistry consistent with the guidelines of green chemistry are proposed.

Toward a More Sustainable Sample Preparation in Phytochemistry: Case Studies in Four Subclasses of Alkaloids

“…7 TAME does not form peroxides during storage, which is a safety advantage over other ethers (e.g., diethyl ether) 11 and avoids the alkaloid artifact formation that can happen when they are solubilized in peroxide-forming ethers, CH 2 Cl 2 , chloroform, and even EtOAc. 23,33 While the synthesis of TAME is achieved via short, atom-efficient, and only moderately energy-consuming processes, EtOAc can be obtained from the reaction of acetic acid with EtOH, both obtained from the fermentation of biomass. 11 Nevertheless, if TAME or EtOAc is not available in a laboratory warehouse, n-butyl acetate (BuOAc) and anisole (boiling points of 115 and 154 °C, respectively) might be tried in the first LLE step and isopropyl acetate (iPrOAc, 89 °C) in the second LLE step (Figure 2A).…”

“…All these solvents have been indicated elsewhere as a potential greener replacement to undesirable nonpolar solvents commonly used in phytochemistry, as well as in other applications. 23,34 BuOAc is commonly used in the pharmaceutical industry and is considered an inexpensive solvent. 23 Laboratory 1 also extracted alkaloids from leaves of P. boldus (Monimiaceae), a plant traditionally used for treating gastrointestinal and liver disorders.…”

“…23,34 BuOAc is commonly used in the pharmaceutical industry and is considered an inexpensive solvent. 23 Laboratory 1 also extracted alkaloids from leaves of P. boldus (Monimiaceae), a plant traditionally used for treating gastrointestinal and liver disorders. 35 This species is a source of aporphine alkaloids, 2 such as boldine (2), isoboldine, isocorydine, laurotetanine, coclaurine, and reticuline.…”

“…Heptane is safer and has a much lower potential for neurotoxicity than hexane (also commonly employed in the purification of alkaloids), being indicated as an easy replacement for it. 3,23 In laboratory 3, the extraction target was mescaline (4), an alkaloid derived from tyrosine, which is a simple phenylethylamine derivative with psychoactive and hallucinogenic properties. 44,45 The source for mescaline was T. macrogonus var.…”

“…For example, the cost to treat organic solvent waste and/or mitigate environmental and health problems potentially arising from their use should also be considered as discussed elsewhere. 23 ■ EXPERIMENTAL SECTION Chemicals. Boldine (≥98%) and harmine (98%) standards were acquired from Sigma-Aldrich, while vincamine (98%) was obtained from Alfa Aesar.…”