Retrosynthetic Analysis: Planning the Route to Drug Synthesis

Weingart Houdeau^*
*Correspondence: Weingart Houdeau, Department of Chemistry, Tianjin University, Tianjin, China, Email:

Keywords

Retrosynthetic analysis • Drug synthesis • Pharmaceuticals

Introduction

Retrosynthetic analysis is a powerful and systematic approach employed by organic chemists to plan the synthesis of complex molecules, particularly in the field of drug development. This method, first introduced by Nobel laureate Elias James Corey, involves working backward from a target molecule to identify simpler precursor molecules or retrosynthetic intermediates. The process aids chemists in designing efficient and feasible synthetic routes by breaking down the complexity of a molecule into more accessible building blocks. The first step in retrosynthetic analysis is identifying the key functional groups present in the target molecule [1]. These functional groups serve as points of disconnection during the retrosynthetic breakdown. Common functional groups include carbonyls, amines, alcohols and heterocycles. Chemists analyze the reactivity and stability of these groups to plan the retrosynthetic disconnections strategically.

Once the key functional groups are identified, the chemist strategically disconnects the target molecule by breaking specific bonds. This process involves the use of retrosynthetic arrows to indicate where the disconnections occur. The aim is to simplify the complex structure into smaller fragments that can be synthesized individually and then assembled to reconstruct the target compound. After identifying possible disconnections, chemists select appropriate retrosynthetic intermediates that can be readily obtained or synthesized. These intermediates are simpler structures that retain the essential functionalities required for subsequent assembly. The choice of intermediates depends on factors such as synthetic accessibility, cost and overall efficiency. To control the regio-chemistry and stereochemistry during the synthesis of retrosynthetic intermediates, chemists often employ protective groups and selective reactions.

Description

Protective groups shield specific functional groups from unwanted reactions, allowing precise manipulation of the molecule. Selective reactions enable the chemist to introduce desired functional groups at specific positions in a controlled manner. Retrosynthetic analysis is a pivotal tool in the design and planning of drug synthesis routes. By deconstructing complex molecules into simpler intermediates, chemists can navigate the intricate pathways leading to the final pharmaceutical product [2,3]. This strategic approach enhances efficiency, reduces cost and facilitates the synthesis of novel therapeutic agents. As the field of organic chemistry continues to advance, retrosynthetic analysis remains a cornerstone technique, empowering researchers in their quest to develop innovative and life-changing pharmaceuticals. Retrosynthetic analysis, as discussed earlier, is employed to plan the synthetic route for the target compound. By working backward from the final product to simpler building blocks, chemists design efficient and practical synthetic routes. This process is crucial for scalability, cost-effectiveness and the overall feasibility of large-scale production.

The development of novel and impactful chemical compounds is a dynamic and multidisciplinary endeavor that encompasses various fields of science and technology. These compounds, which often include pharmaceuticals, agrochemicals, materials and catalysts, play crucial roles in advancing healthcare, agriculture and industry. The process of discovering and designing such compounds involves a combination of innovative strategies, advanced technologies and collaborative efforts [4,5]. For pharmaceutical compounds, successful candidates progress to clinical trials, where their safety and efficacy are tested in human subjects. Regulatory approval and market access are critical milestones that pave the way for the compound to have a meaningful impact on healthcare.

Conclusion

In conclusion, retrosynthetic analysis is a sophisticated yet essential tool in organic chemistry, providing a systematic framework for planning the synthesis of complex molecules. By breaking down intricate structures into more manageable fragments, chemists can navigate the synthesis of diverse compounds, including pharmaceuticals, agrochemicals and other specialty chemicals. This method continues to be a cornerstone in the development of novel and impactful chemical compounds. The development of novel and impactful chemical compounds is a multifaceted process that combines scientific ingenuity, technological advancements and collaborative efforts across disciplines. From target identification to regulatory approval, researchers navigate a complex journey to bring compounds that address critical challenges and improve various aspects of our lives. The continuous pursuit of innovation in compound development is essential for addressing emerging needs and advancing the frontiers of science and technology.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Paydas, Semra. "Management of adverse effects/toxicity of ibrutinib." Crit Rev Oncol Hematol 136 (2019): 56-63.

Google Scholar, Crossref, Indexed at

2. Wu, Jingjing, Christina Liu, Stella T. Tsui and Delong Liu. "Second-generation inhibitors of Bruton tyrosine kinase." J Hematol Oncol 9 (2016): 1-7.

Google Scholar, Crossref, Indexed at

3. Perutelli, Francesca, Maria Chiara Montalbano, Elia Boccellato and Marta Coscia, et al. "Beyond ibrutinib: Novel BTK inhibitors for the treatment of chronic lymphocytic leukemia." Curr Opin Oncol 34 (2022): 757-767.

Google Scholar, Crossref, Indexed at

4. Zain, Rula and Mauno Vihinen. "Structure-function relationships of covalent and non-covalent BTK inhibitors." Front Immunol 12 (2021): 694853.

Google Scholar, Crossref, Indexed at

5. Rozkiewicz, Dariusz, Justyna Magdalena Hermanowicz, Iwona Kwiatkowska and Anna Krupa, et al. "Bruton’s Tyrosine Kinase Inhibitors (BTKIs): Review of Preclinical Studies and Evaluation of Clinical Trials." Molecules 28 (2023): 2400.

Google Scholar, Crossref, Indexed at