Semisynthetic
Encyclopedia
"Semisynthesis" or partial chemical synthesis is a type of chemical synthesis
that uses compounds isolated from natural sources (e.g. plant
material or bacteria
l or cell culture
s) as starting materials. These natural biomolecule
s are usually large and complex molecule
s. This is opposed to a total synthesis
where large molecules are synthesized from a stepwise combination of small and cheap (usually petrochemical) building blocks.
Semisynthesis is usually used when the precursor molecule is too structurally complex, too costly or too inefficient to be produced by total synthesis
. It is also possible that the semisynthetic derivative outperforms the original biomolecule itself with respect to potency, stability or safety.
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 derived from naturally occurring artemisinin
. The latter is unstable due to the presence of a lactone
group and therefore this group is replaced by an acetal
through organic reduction with potassium borohydride and methoxylation
:
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
that uses compounds isolated from natural sources (e.g. plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
material or bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l or cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
s) as starting materials. These natural biomolecule
Biomolecule
A biomolecule is any molecule that is produced by a living organism, including large polymeric molecules such as proteins, polysaccharides, lipids, and nucleic acids as well as small molecules such as primary metabolites, secondary metabolites, and natural products...
s are usually large and complex molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
s. This is opposed to a total synthesis
Total synthesis
In organic chemistry, a total synthesis is, in principle, the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes. In practice, these simpler pieces are commercially available in bulk and semi-bulk quantities, and are often...
where large molecules are synthesized from a stepwise combination of small and cheap (usually petrochemical) building blocks.
Semisynthesis is usually used when the precursor molecule is too structurally complex, too costly or too inefficient to be produced by total synthesis
Total synthesis
In organic chemistry, a total synthesis is, in principle, the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes. In practice, these simpler pieces are commercially available in bulk and semi-bulk quantities, and are often...
. It is also possible that the semisynthetic derivative outperforms the original biomolecule itself with respect to potency, stability or safety.
Drugs derived from natural sources are usually produced by harvesting the natural source or through semisynthetic methods: one example is the semisynthesis of LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
from ergotamine, which is isolated from ergot
Ergot
Ergot or ergot fungi refers to a group of fungi of the genus Claviceps. The most prominent member of this group is Claviceps purpurea. This fungus grows on rye and related plants, and produces alkaloids that can cause ergotism in humans and other mammals who consume grains contaminated with its...
fungus
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
cultures. The commercial production of paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
is also based on semisynthesis (see: paclitaxel total synthesis).
The antimalarial drug artemether
Artemether
Artemether is an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria. It is combined with Lumefantrine and sold by Novartis under the brand names Riamet and Co-Artem.-Chemical nature:...
(a component of Coartem
Coartem
The combination artemether/lumefantrine is an artemisinin-based combination therapy indicated for the treatment of acute uncomplicated plasmodium falciparum malaria. Coartem is produced by the Swiss pharmaceutical company, Novartis.Artemether is a derivative of artemisinin, and lumefantrine is...
) is a semisynthetic derived from naturally occurring artemisinin
Artemisinin
Artemisinin , also known as Qinghaosu , and its derivatives are a group of drugs that possess the most rapid action of all current drugs against falciparum malaria. Treatments containing an artemisinin derivative are now standard treatment worldwide for falciparum malaria...
. The latter is unstable due to the presence of a lactone
Lactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
group and therefore this group is replaced by an acetal
Acetal
An acetal is a molecule with two single-bonded oxygen atoms attached to the same carbon atom.Traditional usages distinguish ketals from acetals...
through organic reduction with potassium borohydride and methoxylation
Methoxy
In chemistry , methoxy refers to the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula O–CH3.The word is used in organic nomenclature usually to describe an ether...
: