The aminocyclitols are compounds related to

cyclitol In organic chemistry, a cyclitol is a cycloalkane containing at least three hydroxyl, each attached to a different ring carbon atom. The general formula for an unsubstituted cyclitol is or where 3 ≤ ''x'' ≤ ''n''. The name is also used for ...

s. They possess features of relative and absolute configuration that are characteristic of their class and have been extensively studied; but these features are not clearly displayed by general methods of stereochemical nomenclature, so that special methods of specifying their configuration are justified and have long been used. In other than stereochemical respects, their nomenclature should follow the general rules of

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...

Aminocyclitol natural products

The aminocyclitol family of

natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical s ...

s is a class of sugar-derived microbial

secondary metabolite Secondary metabolites, also called ''specialised metabolites'', ''secondary products'', or ''natural products'', are organic compounds produced by any lifeform, e.g. bacteria, archaea, fungi, animals, or plants, which are not directly involved ...

s that demonstrate significant biological activities. Aminocyclitols are found as a component of

aminoglycoside Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

which is also called as pseudosugars or pseudosaccharides. Aminocyclitols have chemical structures of a carbon ring with

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

(s). The class of aminocyclitol containing natural products can be divided by ring sizes or types of precursors.

Five-membered ring aminocyclitols

pactamycin

Six-membered ring aminocyclitols

* 2-deoxy-''scyllo''-inosose derived aminoglycosides This class includes

kanamycin Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamy ...

neomycin Neomycin, also known as framycetin, is an aminoglycoside antibiotic that displays bactericidal activity against Gram-negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective against ...

gentamicin Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis amo ...

, apramycin,

hygromycin Hygromycin may refer to either of two chemically dissimilar antibiotics produced by the bacterium ''Streptomyces hygroscopicus'': * Hygromycin A * Hygromycin B, an aminoglycoside that kills bacteria, fungi and higher eukaryotic The eukaryot ...

. * ''myo''-inositol 1-phosphate derived aminoglycosides This class includes

streptomycin Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, Mycobacterium avium complex, ''Mycobacterium avium'' complex, endocarditis, brucellosis, Burkholderia infection, ''Burkholderia'' i ...

spectinomycin Spectinomycin, sold under the tradename Trobicin among others, is an antibiotic useful for the treatment of gonorrhea infections. It is given by injection into a muscle. Common side effects include pain at the area of injection, rash, nausea, ...

. * sedoheptulose 7-phosphate derived C7N aminocyclitol natural products This class includes

acarbose Acarbose ( INN) is an anti-diabetic drug used to treat diabetes mellitus type 2 and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay ( Bayer AG), in North America as Precose ( Bayer Pharmaceuticals), and in ...

validamycin Validamycin is an antibiotic and fungicide produced by ''Streptomyces hygroscopicus''. It is used as an inhibitor of trehalase. It is used for the control of sheath blight of rice and damping-off of cucumbers. See also *Ralstonia solanacearum ...

, validoxylamine A, salbostatin, cetoniacytone A, pyralomicin 1a, kirkamide

Biosynthesis of C7N aminocyclitols

Sedoheptulose 7-phosphate Sedoheptulose 7-phosphate is an intermediate in the pentose phosphate pathway. It is formed by transketolase and acted upon by transaldolase. Sedoheptulokinase is an enzyme that uses sedoheptulose and ATP to produce ADP and sedoheptulose 7-pho ...

, a

pentose phosphate pathway The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt or HMP shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (five-carbon sugars) as well as ribose 5-ph ...

intermediate, is a common precursor of C7N aminocyclitol moiety of natural products, such as

A, salbostatin, cetoniacytone A, and pyralomicin 1a. 2-epi-5-epi-valiolone synthase (EEVS), one of the sugar phosphate cyclase family enzyme and which is a homolog of

3-dehydroquinate synthase The enzyme 3-dehydroquinate synthase (EC 4.2.3.4) catalysis, catalyzes the chemical reaction :3-deoxy-D-''arabino''-hept-2-ulosonate 7-phosphate \rightleftharpoons 3-dehydroquinate + phosphate The protein uses Nicotinamide adenine dinucleotide ...

shikimate pathway The shikimate pathway (shikimic acid pathway) is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (tryptophan, phenylalanine, and tyrosine) ...

, catalyzes the formation of a common intermediate, 2-epi-5-epi-valiolone from

sedoheptulose 7-phosphate Sedoheptulose 7-phosphate is an intermediate in the pentose phosphate pathway. It is formed by transketolase and acted upon by transaldolase. Sedoheptulokinase is an enzyme that uses sedoheptulose and ATP to produce ADP and sedoheptulose 7-pho ...

. After multiple enzyme reaction steps, which include

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

epimer In stereochemistry, an epimer is one of a pair of diastereomers. The two epimers have opposite configuration at only one stereogenic center out of at least two. All other stereogenic centers in the molecules are the same in each. Epimerization is t ...

ization,

dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...

, and keto-reduction reactions,

valienol Valienol (streptol) is a C-7 cyclitol In organic chemistry, a cyclitol is a cycloalkane containing at least three hydroxyl, each attached to a different ring carbon atom. The general formula for an unsubstituted cyclitol is or where 3 ≤ ''x ...

, an important core structure is formed which leads to the formation of C7N aminocyclitol containing natural products. In

biosynthesis, the C-N linkage which connect the C7 cyclitol moiety to the other was found to be formed by unprecedented actions of

nucleotidyltransferase Nucleotidyltransferases are transferase enzymes of phosphorus-containing groups, e.g., substituents of nucleotidylic acids or simply nucleoside monophosphates. The general reaction of transferring a nucleoside monophosphate moiety from A to B, ca ...

and

glycosyltransferase Glycosyltransferases (GTFs, Gtfs) are enzymes ( EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar (also known as the "glycosyl donor") to a nucleophilic gl ...

-like enzymes (which is termed pseudoglycosyltransferase).

References

{{Reflist Cyclitols