Editing Semisynthesis

{{Short description|Type of chemical synthesis}}
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'''Semisynthesis''', or '''partial chemical synthesis''', is a type of [[chemical synthesis]] that uses [[chemical compound]]s isolated from [[natural source]]s (such as [[microbiology|microbial]] cell cultures or [[plant]] material) as the starting materials to produce novel compounds with distinct chemical and medicinal properties. The novel compounds generally have a high [[molecular weight]] or a complex molecular structure, more so than those produced by [[total synthesis]] from simple starting materials. Semisynthesis is a means of preparing many medicines more cheaply than by total synthesis since fewer chemical steps are necessary.

[[Image:Semisynthese taxol.svg|thumb|right|400px|alt=|'''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.<ref name=Goodman/>]]
[[Image:ArtemetherSynthesis.png|thumb|right|400px|alt=|An undesirable [[lactone]] ring in [[artemisinin]] is replaced by an [[acetal]] by [[organic reduction|reduction]] with [[potassium borohydride]], followed by [[methoxy]]lation.<ref name=BoehmOPRD07/>]]

Drugs derived from natural sources are commonly produced either by isolation from their natural source or, as described here, through semisynthesis of an isolated agent. From the perspective of [[chemical synthesis]], [[living organisms]] act as highly efficient chemical factories, capable of producing structurally complex compounds through [[biosynthesis]]. In contrast, engineered chemical synthesis, although powerful, tends to be simpler and less chemically diverse than the complex biosynthetic pathways essential to life.

== Biological vs engineered pathways ==
Due to these differences, certain [[functional groups]] are easier to synthesize using engineered chemical methods, such as [[acetylation]]. However, biological pathways are often able to generate complex groups and structures with minimal economic input, making certain biosynthetic processes far more efficient than total synthesis for producing complex molecules. This efficiency drives the preference for natural sources in the preparation of certain compounds, especially when synthesizing them from simpler molecules would be cost-prohibitive.

== Applications ==
[[Plants]], [[animals]], [[fungi]], and [[bacteria]] are all valuable sources of complex [[reactant|precursor molecules]], with [[bioreactors]] representing an intersection of biological and engineered synthesis. In drug discovery, semisynthesis is employed to retain the medicinal properties of a natural compound while modifying other molecular characteristics—such as [[side effect|adverse effects]] or oral [[bioavailability]]—in just a few chemical steps. Semisynthesis contrasts with [[total synthesis]], which constructs the target molecule entirely from inexpensive, low-molecular-weight precursors, often petrochemicals or minerals.<ref name="rsc.org">{{cite web|url=http://prospect.rsc.org/blogs/cw/2013/10/28/trouble-and-strife-total-synthesis/|title=Welcome to Chemistry World|website=Chemistry World}}</ref> While there is no strict boundary between total synthesis and semisynthesis, they differ primarily in the degree of engineered synthesis employed. Complex or fragile functional groups are often more cost-effective to extract directly from an organism than to prepare from simpler precursors, making semisynthesis the preferred approach for complex natural products.

== Notable examples in drug development ==
Practical applications of semisynthesis include the groundbreaking isolation of the antibiotic [[chlortetracycline]] and the subsequent semisynthesis of antibiotics such as [[tetracycline]], doxycycline, and [[tigecycline]].<ref name=Tetrahist>{{cite journal | vauthors = Nelson ML, Levy SB | title = The history of the tetracyclines | journal = Annals of the New York Academy of Sciences | volume = 1241 | issue = December | pages = 17–32 | date = December 2011 | pmid = 22191524 | doi = 10.1111/j.1749-6632.2011.06354.x | s2cid = 34647314 | bibcode = 2011NYASA1241...17N }}</ref><ref name=MyersPlatformHist>{{cite journal | vauthors = Liu F, Myers AG | title = Development of a platform for the discovery and practical synthesis of new tetracycline antibiotics | journal = Current Opinion in Chemical Biology | volume = 32 | pages = 48–57 | date = June 2016 | pmid = 27043373 | doi = 10.1016/j.cbpa.2016.03.011 | doi-access = free }}</ref> Other notable examples include the early commercial production of the anti-cancer agent [[paclitaxel total synthesis|paclitaxel]] from 10-deacetylbaccatin, isolated from ''[[Taxus baccata]]'' (European yew),<ref name=Goodman>{{cite book| vauthors = Goodman J, Walsh V |title=The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug|url={{google books |plainurl=y |id=vHOOcw4buKoC}}|date=5 March 2001|publisher=Cambridge University Press|isbn=978-0-521-56123-5 | pages = 100f}}</ref> the semisynthesis of [[LSD]] from [[ergotamine]] (derived from fungal cultures of [[ergot]]),{{citation needed|date=March 2017}} and the preparation of the antimalarial drug [[artemether]] from the naturally occurring compound [[artemisinin]].<ref name=BoehmOPRD07>{{cite journal |vauthors=Boehm M, Fuenfschilling PC, Krieger M, Kuesters E, Struber F | date = 2007 | title = An Improved Manufacturing Process for the Antimalaria Drug Coartem. Part I | journal = Org. Process Res. Dev.| volume = 11 | issue = 3 | pages = 336–340 | doi=10.1021/op0602425}}</ref>{{primary source inline|date=March 2017}}{{primary source inline|date=March 2017}} As synthetic chemistry advances, transformations that were previously too costly or difficult to achieve become more feasible, influencing the economic viability of semisynthetic routes.<ref name="rsc.org"/>

== See also ==
*[[Chemurgy]]
*[[Drug discovery]]
*[[Drug development]]
*[[Phytomining]]
*Production of cephalopsporins from [[7-ACA]]
*Production of penicillins from [[6-APA]]
*Production of steroids from [[16-Dehydropregnenolone Acetate|16-DPA]]
*Production of [[ursodeoxycholic acid]] from cholic acid

== References ==
{{reflist|3}}

{{chemical synthesis}}
{{Branches of chemistry}}

[[Category:Chemical synthesis]]
[[Category:Medicinal chemistry]]