4.8 Review

Green Chemistry in the Synthesis of Pharmaceuticals

Journal

CHEMICAL REVIEWS
Volume 122, Issue 3, Pages 3637-3710

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrev.1c00631

Keywords

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Funding

  1. National Science Foundation [NSF/CREST HRD-1547754, NSF/RISE HRD-1547836]
  2. European Commission [LIFE16 ENV/IT/000167]

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The principles of green chemistry can be effectively implemented in the green synthesis of pharmaceuticals by choosing solvent-free or green solvents, considering one-pot synthesis, multicomponent reactions, continuous processing, and process intensification approaches. Researchers and industries are actively pursuing green synthesis processes to control waste reduction and protect the environment.
The principles of green chemistry (GC) can be comprehensively implemented in green synthesis of pharmaceuticals by choosing no solvents or green solvents (preferably water), alternative reaction media, and consideration of one-pot synthesis, multicomponent reactions (MCRs), continuous processing, and process intensification approaches for atom economy and final waste reduction. The GC's execution in green synthesis can be performed using a holistic design of the active pharmaceutical ingredient's (API) life cycle, minimizing hazards and pollution, and capitalizing the resource efficiency in the synthesis technique. Thus, the presented review accounts for the comprehensive exploration of GC's principles and metrics, an appropriate implication of those ideas in each step of the reaction schemes, from raw material to an intermediate to the final product's synthesis, and the final execution of the synthesis into scalable industry-based production. For real-life examples, we have discussed the synthesis of a series of established generic pharmaceuticals, starting with the raw materials, and the intermediates of the corresponding pharmaceuticals. Researchers and industries have thoughtfully instigated a green synthesis process to control the atom economy and waste reduction to protect the environment. We have extensively discussed significant reactions relevant for green synthesis, one-pot cascade synthesis, MCRs, continuous processing, and process intensification, which may contribute to the future of green and sustainable synthesis of APIs.

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