semisynthetiques

Semisynthetiques refer to chemical compounds produced by partial chemical modification of natural products. They occupy a middle ground between purely natural substances and fully synthetic molecules, combining a known biological scaffold with deliberate chemical changes to alter properties.

In practice, semisynthesis starts with a natural product produced by a microorganism or plant and then introduces targeted chemical changes. Modifications can involve changing side chains, ring substituents, or protecting groups to broaden the range of activity, improve stability or oral bioavailability, or increase resistance to metabolic degradation. The approach allows refinement of pharmacological properties without building a completely new molecule from scratch.

Examples and scope often focus on antibiotics, where semisynthesis has yielded widely used drugs. Semisynthetic penicillins such as ampicillin, amoxicillin, oxacillin, and cloxacillin extend spectrum or improve stability and resistance to degradation. Semisynthetic cephalosporins—including cephalexin, cefuroxime, and ceftriaxone—are derived from natural cephalosporin cores with modified side chains. In the macrolide class, derivatives like clarithromycin and azithromycin are produced semisynthetically from erythromycin. The concept also encompasses other drug families that rely on natural templates, modified to enhance clinical properties.

Advantages of semisynthesis include the ability to tailor pharmacokinetics and spectrum of activity using established scaffolds, potentially reducing development time and cost. Limitations involve dependence on the natural core, possible resistance pathways, and manufacturing or regulatory considerations.

Historically, semisynthesis has been a central strategy in pharmaceutical development since the mid-20th century and remains a common approach alongside wholly natural-product discovery and total synthesis.