Page 203 - CW E-Magazine (3-12-2024)

Special Report Special Report

Green Chemistry from a pharmaceuticals industry is occasionally contradictory, as industry has made tremendous use of cleavage of penicillin G is performed in
multiple criteria lead to its green status. biocatalytic processes in small drug water at 37°Cwith only NH (0.09-kg/
3
perspective Still, the major factors should be safety, molecule discovery. Biocatalysis has kg of 6-APA) as a reagent, used to
occupational health, quality (risk and also been integrated into mainstream adjust the pH.
hemicals are useful in our daily vaccines to prevent and treat disease. PROF. BHALCHANDRA M. BHANAGE number of impurities), utilization of organic synthesis particularly for the
lives in several ways, and they During drug development utmost care Head, Department of Chemistry & complete reagent, recyclability issues, enantioselective synthesis of APIs, as Multicomponent reactions (MCRs)
Ccan be produced using diffe- is taken to try and select materials that Professor of Industrial and and industrial constraints (e.g., atom many exist as enantiomers. The asym- MCR scan be defi ned as one-pot
rent manufacturing processes that have have less environmental impact, reduce Engineering Chemistry economy, freezing temperature, boiling metric synthesis of enantiomeric chiral chemical reactions among three or
fewer negative effects on the environ- the use of resources, minimize waste, Institute of Chemical Technology, point, recyclability, density). Therefore, compounds can be done with a series more substrates in a highly regio- and
ment, human health, and society. In the and run safe processes. While patients Mumbai solvents can be selected wisely and of enzymes with outstanding selectivity stereoselective manner to deliver a
1960s, chemists from different indus- may only see the end results of drug Email: bm.bhanage@gmail.com used in a limited amount. That means and specifi city profi les. structurally complex single organic
tries worked to refi ne chemical produc- development, pharmaceutical companies that solvents with known hazardous molecule that retains all or most of the
tion in environmentally benign way. The have been increasing their focus on a holistic design of the active pharma- characteristics need to be omitted as Biocatalysis offers the following atoms of the starting materials. Thus,
term coined by the United States Environ- reducing environmental impact. A transi- ceutical ingredient’s (APIs) life cycle, much as possible either by altering the benefi ts over traditional routes: signi- considering atom economy and waste
mental Protection Agency was Green tion towards a sustainable future will minimizing hazards and pollution, and synthesis process or by substituting the fi cantly reduced waste; more atom and reduction, the involvement of MCRs
Chemistry (GC) and defi ned as “the de- require the use of greener technologies that capitalizing the resource effi ciency in solvents with non-hazardous or less step economy; low environmental haz- in the synthesis of pharmaceuticals can
sign of chemical products and processes change the way we manage the entire the synthesis technique. hazardous solvents. ards; safer solvents and auxiliaries, as help in green and sustainable process.
that reduce or eliminate the generation chemical lifecycles, from chemical sup- the process is usually performed in wa-
of hazardous substances(1).” ply chains and chemical manufacturing Solvent selection One of the additional problems for ter; energy-effi cient; evading the need Under MCRs, the fi nal product is
to use and end-life of fi nal products(2). In the synthesis process of any drug, pharmaceutical companies are the new for functional group activation and cir- constructed as per the cascade of ele-
GC applies across the life cycle of half of the reagents used are solvents, and regulations concerning environmental cumventing the protection and deprot- mentary chemical reactions that main-
a chemical product, including its de- The 12 Principles of GC can be they have the largest contribution to API pollution of water sources, from both ection steps; and mild and safe condi- tain a network of reaction equilibria.
sign, manufacture, use, and ultimate implemented in the green synthesis of waste, carbon footprint, and energy use. industrial waste as well as from the tions (pH and temperature). Therefore, the fl ow of the reaction is
disposal. It is a philosophy that applies pharmaceuticals by choosing no solvents Thus, restricting their use and selecting traces of the drugs and medicinal pro- irreversible, and the amount of yield is
to all areas of chemistry, not a single or green solvents (preferably water), suitable solvents or the “greenest” ones ducts released as municipal liquid waste. Among the enzymes, oxidoreduc- close to 100% most of the time. MCRs
discipline of chemistry. It applies inno- alternative reaction media (e.g.,ionic allows one to achieve substantial sav- It has been found that even low concen- tase, ketoreductase, diketoreducatase, can be performed in a one-pot version
vative scientifi c solutions to real-world liquids, supercritical carbon dioxide), and ings in the environmental impact of any trations of drugs and drug metabolites amino acid dehydrogenases, trans- and the major byproduct(s) from an
environmental problems and results in consideration of one-pot synthesis, multi- pharmaceutical synthesis. Additionally, heavily pollute lakes, rivers, and coastal minases, α-transminase, lipase, protease, MCR is water.
source reduction because it prevents the component reactions (MCRs), conti- using as few solvents as possible in the regions. Drugs in higher concentra- adolase, and nitrile hydratasephenyl-
generation of pollution. It also reduces nuous processing, and process intensifi - process is a green design criterion, as it tions severely affect aquatic organisms alanine-ammonia-lyase have seen MCRs have multiple advantages
the negative impacts of chemical pro- cation approaches for atom economy and facilitates solvent recycling. like fi sh, and other benthic organisms. widespread use in the pharmaceutical over the stepwise linear synthetic pro-
ducts and processes on human health fi nal waste reduction. GC’s execution in Mostly, pharmaceutical manufacturers industry. cess, such as atom economy, time &
and the environment and lessens and green synthesis can be performed using The choice of the “greenest” solvent are attentive of these facts and take the energy economies, less waste genera-
sometimes eliminates hazards from Table 1: Solvent selection guide environmental problems very seriously. Enzymatic processes have a great tion, one-pot synthesis, less human
existing products and processes. It designs Preferred Usable Undesirable capacity for one-pot cascades, as reac- effort & resources requirement, easy
chemical products and processes to Water Cyclohexane Pentane Green feedstocks tion conditions tend to be more com- purifi cation issues, mild conditions, high
reduce their intrinsic hazards. Acetone Heptane Hexane(s) A major issue with application of parable than for classical chemical convergence, and high yield of the fi nal
Ethanol Toluene Di-isopropyl ether green synthesis is that green feedstocks reactions. For example, 6-amino- product. Although MCRs are quite popu-
Nowadays, GC has gone beyond 2-Propanol Methylcyclohexane Diethyl ether are not easily accessible. This is because penicillanic acid (6-APA) is a major raw lar among combinatorial & medicinal
being laboratory scale, and entered into 1-Propanol TBME Dichloromethane either they are not at the correct level, material for preparing semi-synthetic chemists, agro-chemists, and polymer
large-scale applications in industries. Ethyl acetate Isooctane Dichloroethane i.e. too detailed or too basic, or it is penicillins and cephalosporins, by scientists, the awareness to use them in
These changes in terms of innovative Isopropyl acetate Acetonitrile Chloroform diffi cult to fi nd them. Sometimes they hydrolysis of penicillin G. Previously, a sustainability and GC is questionable.
ideas, feedstocks, safer raw materials, Methanol 2-MeTHF NMP are not in a user-friendly format or not chemical procedure for the hydrolysis Such benefi ts as diversity-oriented syn-
and alternative mechanisms at pilot industry-specifi c. involved an environmentally hazardous thesis, combinatorial library genera-
scale seems fascinating to apply in MEK THF DMF chlorinated hydrocarbon solvent tion, and convergence/divergence
industries. 1-Butanol Xylenes Pyridine Biocatalysis (CH Cl ), and a reaction temperature acknowledge many aspects of GC and
2
2
t-Butanol DMSO DMAc Biological catalysts or enzymes gen- of -40°C. To produce 1-kg of 6-APA, the sustainable synthesis process.
For the pharmaceutical industry, scCO 2 Acetic acid Dioxane erated from living systems (microbial 1.2-kg of PCl , 0.6-kg of Me SiCl,
3
5
scientifi c innovation begins in the lab, Ethylene glycol Dimethoxyethane enzymes) are being used to carry out 0.2-kg of NH , 1.6-kg of PhNMe , 8.4-l For the purpose of green synthesis,
3
2
wherein chemistry is foundational to Benzene reactions between organic components. of CH Cl , and 8.4-l of n-BuOH were well-known classical MCRs are
2
2
designing and delivering medicines and Carbon tetrachloride Over the years, the pharmaceutical required. On the contrary, the enzymatic Biginelli, Strecker, Mannich, Passerini, Ugi,
202 Chemical Weekly December 3, 2024 Chemical Weekly December 3, 2024 203
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