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Total synthesis
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{{Short description|Complete chemical synthesis of a complex molecule}} {{cs1 config|name-list-style=vanc|display-authors=6}} <!--When editing this page, it is important to qualify sources. There is a lot of "soft info" known in the synthesis community that is difficult to cite, and it is tempting to include it. Please avoid this as this page has historically been handwavy with unqualifiable insider knowledge the public cannot cross check.--> '''Total synthesis''', a specialized area within [[organic chemistry]], focuses on constructing complex organic compounds, especially those found in nature, using laboratory methods.<ref name=nature /><ref name=Nicolaou1 /><ref name=Nicolaou2 /><ref name=Nicolaou3 /> It often involves synthesizing [[natural product]]s from basic, commercially available starting materials. Total synthesis targets can also be [[organometallic]] or [[inorganic]].<ref name="Inorganic synth">{{cite journal | vauthors = Buck MR, Schaak RE | title = Emerging Strategies for the Total Synthesis of Inorganic Nanostructures | journal = Angewandte Chemie | volume = 52 | issue = 24 | pages = 6154–6178 | date = June 2013 | pmid = 23610005 | doi = 10.1002/anie.201207240 }}</ref><ref name=RBW1963>{{cite journal|doi=10.1002/ange.19630751827|title=Versuche zur Synthese des Vitamins B<sub>12</sub>|journal=Angewandte Chemie|volume=75|issue=18|pages=871–872|date=1963| vauthors = Woodward RB |bibcode=1963AngCh..75..871W|author-link1=Robert Burns Woodward}}</ref> 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.<ref>{{cite journal | last1 = Eichberg | first1 = Michael J. | last2 = Dorta | first2 = Rosa L. | last3 = Grotjahn | first3 = Douglas B. | last4 = Lamottke | first4 = Kai | last5 = Schmidt | first5 = Martin | last6 = Vollhardt | first6 = K. Peter C. | year = 2001 | title = Approaches to the Synthesis of (±)-Strychnine via the Cobalt-Mediated [2 + 2 + 2] Cycloaddition: Rapid Assembly of a Classic Framework | journal = [[J. Am. Chem. Soc.]] | volume = 123 | issue = 38| pages = 9324–9337 | doi = 10.1021/ja016333t | pmid = 11562215 | bibcode = 2001JAChS.123.9324E }}</ref> Similarly, in [[chemical biology]], it provides research tools for studying biological systems and processes.<ref>{{citation|author=Stéphane Helleboid, Christian Haug, Kai Lamottke, Yijun Zhou, Jianbing Wei, Sébastien Daix, Linda Cambula, Géraldine Rigou, Dean W. Hum, Robert Walczak |date=2014 |doi=10.1177/1087057113497095 |issue=3 |pages=399–406 |periodical=SLAS Discovery |pmid=23896689 |title=The Identification of Naturally Occurring Neoruscogenin as a Bioavailable, Potent, and High-Affinity Agonist of the Nuclear Receptor RORα (NR1F1) |volume=19|doi-access=free }}<!-- auto-translated from German by Module:CS1 translator --></ref> Additionally, synthesis aids natural product research by helping confirm and elucidate the structures of newly isolated compounds.<ref name=Lamottke>{{citation|author=Michael Müller, Kai Lamottke, Erich Löw, Eva Magor-Veenstra, Wolfgang Steglich |date=2000 |issue=15 |pages=2483-2489. https://doi.org/10.1039/B003053H |periodical=Journal of the Chemical Society, Perkin Transactions 1 |title=Stereoselective total syntheses of atrochrysone, torosachrysone and related 3, 4-dihydroanthracen-1 (2 H)-ones|doi=10.1039/B003053H }}<!-- auto-translated from German by Module:CS1 translator --></ref><ref>{{citation|author=Michael Müller, Kai Lamottke, Wolfgang Steglich, Stefan Busemann, Matthias Reichert, Gerhard Bringmann, Peter Spiteller |date=2004 |pages=4850–4855 |doi=10.1002/ejoc.200400518 |periodical=European Journal of Organic Chemistry |title=Biosynthesis and Stereochemistry of Phlegmacin-Type Fungal Pigments|issue=23 }}</ref> 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.<ref name=armaly /> 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.<ref name="Fay_2023">{{cite journal | vauthors = Fay N, Kouklovsky C, de la Torre A | title = Natural Product Synthesis: The Endless Quest for Unreachable Perfection | journal = ACS Organic & Inorganic Au | volume = 3 | issue = 6 | pages = 350–363 | date = December 2023 | pmid = 38075446 | doi = 10.1021/acsorginorgau.3c00040 | pmc = 10704578 }}</ref>
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