Protecting‐Group‐Free Synthesis of Drugs and Pharmaceuticals

Ramesh, Remya; Sonawane, Swapnil P.; Reddy, D. Srinivasa; Bandichhor, Rakeshwar

doi:10.1002/9781119295266.ch6

Cited by 3 publications

(2 citation statements)

References 57 publications

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“…The application of chemoselective synthetic strategies, specifically protecting-group-free methods, offers substantial benefits in the development of sustainable, cost-effective, and operationally simple manufacturing processes. 16,39,40 This aligns with one of the 12 green https://doi.org/10.26434/chemrxiv-2023-d4nxn ORCID: https://orcid.org/0000-0002-2664-4491 Content not peer-reviewed by ChemRxiv. License: CC BY 4.0 chemistry principles, 2 which encourages the avoidance of unnecessary derivatization.…”

Section: Introductionsupporting

confidence: 64%

Protecting-Group-Free Mechanosynthesis of Amides from Hydroxycarboxylic Acids: Application to the Synthesis of Imatinib

Nikonovich,

Jarg,

Martõnova

et al. 2023

Preprint

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Mechanochemical methods for assembling carbon-nitrogen bonds play a central role in the ongoing green chemistry-driven renovation of organic synthesis, including the synthesis of active pharmaceutical ingredients (APIs). However, chemoselective issues in these transformations, such as the tolerance of unmasked hydroxyl groups, have not been systematically explored. Screening of various amide coupling conditions revealed that 1 ethyl 3 (3 dimethylaminopropyl)carbodiimide (EDC) in combination with ethyl acetate as a liquid-assisted grinding (LAG) solvent was the most selective amide coupler, delivering 76–94% yields of the respective amide products from unprotected hydroxycarboxylic acids. Boc-protected tyrosine and serine with unmasked hydroxyl functionalities were successfully involved in peptide couplings. By incorporating green chemistry principles as a driver for innovation, the established protocol was applied to the synthesis of imatinib, an anticancer drug included in the World Health Organization’s List of Essential Medicines. The target API was synthesized with an overall yield of 86% and 99% HPLC purity through a two-step mechanochemical C–N bond assembling reaction sequence starting from 4 (hydroxymethyl)benzoic acid. A comparison of green chemistry metrics between the developed mechanochemical approach and similar solution-based approaches revealed reduced waste generation, enhanced eco-friendliness, and a superior safety profile for the proposed strategy. The safety improvement was primarily attributed to the elimination of toxic solvents and a genotoxic intermediate from the production chain.

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Section: Introductionsupporting

confidence: 64%

Protecting-Group-Free Mechanosynthesis of Amides from Hydroxycarboxylic Acids: Application to the Synthesis of Imatinib

Nikonovich,

Jarg,

Martõnova

et al. 2023

Preprint

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“…The protecting-group-free synthesis of drugs or active pharmaceutical ingredients is a great challenge. 24 Due to the presence of many hydroxyl groups, the reduction of protection-deprotection steps is even more challenging for the preparation of nucleoside analogues. To the best of our knowledge, there is currently no chemical protecting-group-free synthesis of biologically active fluorinated nucleosides.…”

Section: Introductionmentioning

confidence: 99%

Protecting-group-free synthesis of clevudine (l-FMAU), a treatment of the hepatitis B virus

2022

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Synthesis of Lincosamide Analogues via Oxime Resin Aminolysis

Tremblay

Haguette

Robert-Scott

et al. 2022

Synlett

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In this work, the synthetic development of an oxime resin aminolysis to lincosamide analogues is described. This synthetic endeavour hinges on a protecting-group-free strategy of the aminosugar nucleophiles. The cleavage from the solid support is achieved under mild condition in a buffer solution and allows the preparation a wide diversity of amino acid moieties onto glycosylamine scaffolds. The strategy is further exploited using methylthiolincosamine to generate rapidly complex lincomycin analogues. The results pave the way to access efficiently novel potentially relevant antibacterial compounds.

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Protecting‐Group‐Free Synthesis of Drugs and Pharmaceuticals

Cited by 3 publications

References 57 publications

Protecting-Group-Free Mechanosynthesis of Amides from Hydroxycarboxylic Acids: Application to the Synthesis of Imatinib

Protecting-Group-Free Mechanosynthesis of Amides from Hydroxycarboxylic Acids: Application to the Synthesis of Imatinib

Protecting-group-free synthesis of clevudine (l-FMAU), a treatment of the hepatitis B virus

Synthesis of Lincosamide Analogues via Oxime Resin Aminolysis

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