Semi-synthesis

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.

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. 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.

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. 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. 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. Elaboration of these precursors by chemical synthesis may then cost-effectively provide a variety of complex final targets.

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