Semisynthesis

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Semisynthesis or partial chemical synthesis is a type of chemical synthesis that uses chemical compounds isolated from natural sources (e.g., microbial cell cultures or plant material) as the starting materials to produce other novel compounds with distinct chemical and medicinal properties. These novel compounds are generally high molecular weight, complex molecule targets, more so than those produced by chemical synthesis from simple starting materials.[citation needed]

Drugs derived from natural sources are usually produced by isolation from the natural source, or, as described here, by semisynthesis from such an isolated agent. From the viewpoint of chemical synthesis, living organisms are remarkable chemical factories, capable of producing structurally complex chemical compounds with ease by biosynthesis, compounds that synthesis by humans would struggle to produce efficiently, if they could be produced at all.[citation needed] In some cases, with a small investment in botany or microbiology, a plant or microorganism can be grown to produce such chemical precursors with a lower commitment in net labour and material costs.[citation needed]

Semisynthesis, when used in drug discovery, aims to retain the sought after medicinal activity while altering other molecule characteristics—for instance, those effecting its adverse events or its oral bioavailability—in a few chemical steps.[citation needed] In this regard, semisynthesis stands in contrast with the approach of natural product total synthesis, where the aim is also to arrive at the complex target, also by step-wise chemical modifications, but to do so beginning with very low molecular weight, inexpensive starting materials, often petrochemicals, but also simple biochemicals; total synthesis of the same molecule afforded by semisynthesis, in contrast, often requires many tens of chemical steps.[citation needed] Hence, methods of semisynthesis are applied when a needed precursor molecule is too structurally complex, too costly, or too difficult to produce by total synthesis.[citation needed] Elaboration of these precursors by chemical synthesis may then cost-effectively provide a variety of complex final targets.

Semisynthesis of Paclitaxel. Installation of the necessary side chain and acetyl group of paclitaxel, by a short series of steps starting from isolated 10-deacetylbaccatine III.[1]
An undesirable lactone ring in artemisinin is replaced by an acetal by reduction with potassium borohydride followed by methoxylation.[2]

Examples of practical application of the use of semisynthesis include in the groundbreaking historic case of the the isolation of the antibiotic chlortetracycline, and the semisyntheses of the further novel antibiotics tetracycline, doxycycline, and tigecycline.[3][4] Further examples of semisynthesis include the early commercial production of anti-cancer agent paclitaxel from 10-deacetylbaccatin isolated from the needles of Taxus baccata (European yew),[1] the prepartion of LSD from ergotamine isolated from fungal cultures of ergot,[citation needed] and the semisynthesis of the antimalarial drug artemether from naturally occurring artemisinin.[2][non-primary source needed]

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References[edit]

  1. ^ a b Goodman, Jordan; Walsh, Vivien (5 March 2001). The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug. Cambridge University Press. pp. 100f. ISBN 978-0-521-56123-5. 
  2. ^ a b Boehm M, Fuenfschilling PC, Krieger M, Kuesters E, Struber, F (2007). "An Improved Manufacturing Process for the Antimalaria Drug Coartem. Part I". Org. Process Res. Dev. 11 (3): 336–340. doi:10.1021/op0602425. [non-primary source needed]
  3. ^ Nelson ML, Levy SB (2011). "The History of the Tetracyclines". Annals of the New York Academy of Sciences. 1241 (December): 17–32. doi:10.1111/j.1749-6632.2011.06354.x. PMID 22191524. 
  4. ^ Liu F, Myers, AG (2016). "Development of a Platform for the Discovery and Practical Synthesis of New Tetracycline Antibiotics" (PDF). Current Opinion in Chemical Biology. 32: 48–57. doi:10.1016/j.cbpa.2016.03.011. 

Continuous Flow Processes for Catalytic Upgrading of Biofeedstocks