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Semisynthesis, orpartial chemical synthesis, is a type ofchemical synthesis that useschemical compounds isolated fromnatural sources (such asmicrobial cell cultures orplant material) as the starting materials to produce novel compounds with distinct chemical and medicinal properties. The novel compounds generally have a highmolecular weight or a complex molecular structure, more so than those produced bytotal 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.
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 ofchemical synthesis,living organisms act as highly efficient chemical factories, capable of producing structurally complex compounds throughbiosynthesis. In contrast, engineered chemical synthesis, although powerful, tends to be simpler and less chemically diverse than the complex biosynthetic pathways essential to life.
Due to these differences, certainfunctional groups are easier to synthesize using engineered chemical methods, such asacetylation. 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.
Plants,animals,fungi, andbacteria are all valuable sources of complexprecursor molecules, withbioreactors 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 asadverse effects or oralbioavailability—in just a few chemical steps. Semisynthesis contrasts withtotal synthesis, which constructs the target molecule entirely from inexpensive, low-molecular-weight precursors, often petrochemicals or minerals.[3] 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.
Practical applications of semisynthesis include the groundbreaking isolation of the antibioticchlortetracycline and the subsequent semisynthesis of antibiotics such astetracycline, doxycycline, andtigecycline.[4][5] Other notable examples include the early commercial production of the anti-cancer agentpaclitaxel from 10-deacetylbaccatin, isolated fromTaxus baccata (European yew),[1] the semisynthesis ofLSD fromergotamine (derived from fungal cultures ofergot),[citation needed] and the preparation of the antimalarial drugartemether from the naturally occurring compoundartemisinin.[2][non-primary source needed][non-primary source needed] As synthetic chemistry advances, transformations that were previously too costly or difficult to achieve become more feasible, influencing the economic viability of semisynthetic routes.[3]
Branches ofchemistry | |
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| Analytical | |
| Theoretical | |
| Physical | |
| Inorganic | |
| Organic | |
| Biological | |
| Interdisciplinarity | |
| See also | |
