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Semisynthesis or partial chemical synthesis is a type of chemical synthesis that uses compounds isolated from natural sources (e.g. plant material or bacterial or cell cultures) as starting materials. These natural biomolecules are often large and complex molecules. This is opposed to a total synthesis where large molecules are synthesized through a stepwise combination of small and inexpensive (usually petrochemical) building blocks.

Semisynthesis is usually used when the precursor molecule is too structurally complex, too costly, or too difficult to be produced by total synthesis. From a synthesis viewpoint, life is capable of biosynthesizing structurally complex chemical compound. In some cases, with a small agricultural investment, a plant can be grown to produce chemical intermediates that chemical synthesis would struggle to produce. Elaboration of these intermediates with synthetic chemistry can then cost-effectively provide the complex final targets.

Drugs derived from natural sources are usually produced by harvesting the natural source or through semisynthetic methods: one example is the semisynthesis of LSD from ergotamine, which is isolated from ergot fungus cultures. The commercial production of paclitaxel is also based on semisynthesis (see paclitaxel total synthesis).

The antimalarial drug artemether (a component of Coartem) is a semisynthetic drug derived from naturally occurring artemisinin. Artemisinin contains an undesirable lactone group and which is replaced by an acetal through organic reduction with potassium borohydride and methoxylation:[1]

Artemether semisynthesis from artemisinin

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  1. ^ An Improved Manufacturing Process for the Antimalaria Drug Coartem. Part IMatthias Boehm, Peter C. Fuenfschilling, Matthias Krieger, Ernst Kuesters, and Fritz Struber Org. Process Res. Dev.; 2007; 11(3) pp 336 - 340; (Article) doi:10.1021/op0602425