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Total synthesis

Total synthesis, a specialized area within organic chemistry, focuses on constructing complex organic compounds, especially those found in nature, using laboratory methods.[1][2][3][4] It often involves synthesizing natural products from basic, commercially available starting materials. Total synthesis targets can also be organometallic or inorganic.[5][6] While total synthesis aims for complete construction from simple starting materials, modifying or partially synthesizing these compounds is known as semisynthesis.

Natural product synthesis serves as a critical tool across various scientific fields. In organic chemistry, it tests new synthetic methods, validating and advancing innovative approaches. In medicinal chemistry, natural product synthesis is essential for creating bioactive compounds, driving progress in drug discovery and therapeutic development.[7] Similarly, in chemical biology, it provides research tools for studying biological systems and processes.[8] Additionally, synthesis aids natural product research by helping confirm and elucidate the structures of newly isolated compounds.[9][10]

The field of natural product synthesis has progressed remarkably since the early 19th century, with improvements in synthetic techniques, analytical methods, and an evolving understanding of chemical reactivity.[11] Today, modern synthetic approaches often combine traditional organic methods, biocatalysis, and chemoenzymatic strategies to achieve efficient and complex syntheses, broadening the scope and applicability of synthetic processes.

Key components of natural product synthesis include retrosynthetic analysis, which involves planning synthetic routes by working backward from the target molecule to design the most effective construction pathway. Stereochemical control is crucial to ensure the correct three-dimensional arrangement of atoms, critical for the molecule's functionality. Reaction optimization enhances yield, selectivity, and efficiency, making synthetic steps more practical. Finally, scale-up considerations allow researchers to adapt lab-scale syntheses for larger production, expanding the accessibility of synthesized products. This evolving field continues to fuel advancements in drug development, materials science, and our understanding of the diversity in natural compounds.[12]

  1. ^ Cite error: The named reference nature was invoked but never defined (see the help page).
  2. ^ Cite error: The named reference Nicolaou1 was invoked but never defined (see the help page).
  3. ^ Cite error: The named reference Nicolaou2 was invoked but never defined (see the help page).
  4. ^ Cite error: The named reference Nicolaou3 was invoked but never defined (see the help page).
  5. ^ Buck MR, Schaak RE (June 2013). "Emerging Strategies for the Total Synthesis of Inorganic Nanostructures". Angewandte Chemie. 52 (24): 6154–6178. doi:10.1002/anie.201207240. PMID 23610005.
  6. ^ Woodward RB (1963). "Versuche zur Synthese des Vitamins B12". Angewandte Chemie. 75 (18): 871–872. Bibcode:1963AngCh..75..871W. doi:10.1002/ange.19630751827.
  7. ^ Eichberg MJ, Dorta RL, Grotjahn DB, Lamottke K, Schmidt M, Vollhardt KP (2001). "Approaches to the Synthesis of (±)-Strychnine via the Cobalt-Mediated [2 + 2 + 2] Cycloaddition: Rapid Assembly of a Classic Framework". J. Am. Chem. Soc. 123 (38): 9324–9337. doi:10.1021/ja016333t. PMID 11562215.
  8. ^ Stéphane Helleboid, Christian Haug, Kai Lamottke, Yijun Zhou, Jianbing Wei, Sébastien Daix, Linda Cambula, Géraldine Rigou, Dean W. Hum, Robert Walczak (2014), "The Identification of Naturally Occurring Neoruscogenin as a Bioavailable, Potent, and High-Affinity Agonist of the Nuclear Receptor RORα (NR1F1)", SLAS Discovery, vol. 19, no. 3, pp. 399–406, doi:10.1177/1087057113497095, PMID 23896689{{citation}}: CS1 maint: multiple names: authors list (link)
  9. ^ Michael Müller, Kai Lamottke, Erich Löw, Eva Magor-Veenstra, Wolfgang Steglich (2000), "Stereoselective total syntheses of atrochrysone, torosachrysone and related 3, 4-dihydroanthracen-1 (2 H)-ones", Journal of the Chemical Society, Perkin Transactions 1, no. 15, pp. 2483-2489. https://doi.org/10.1039/B003053H{{citation}}: CS1 maint: multiple names: authors list (link)
  10. ^ Michael Müller, Kai Lamottke, Wolfgang Steglich, Stefan Busemann, Matthias Reichert, Gerhard Bringmann, Peter Spiteller (2004), "Biosynthesis and Stereochemistry of Phlegmacin‐Type Fungal Pigments", European Journal of Organic Chemistry, pp. 4850–4855, doi:10.1002/ejoc.200400518{{citation}}: CS1 maint: multiple names: authors list (link)
  11. ^ Cite error: The named reference armaly was invoked but never defined (see the help page).
  12. ^ Fay N, Kouklovsky C, de la Torre A (December 2023). "Natural Product Synthesis: The Endless Quest for Unreachable Perfection". ACS Organic & Inorganic Au. 3 (6): 350–363. doi:10.1021/acsorginorgau.3c00040. PMC 10704578. PMID 38075446.

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