The oxathiazolones are a family of

heterocyclic compounds A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

in which the parent derivative has the molecular formula C₂HNO₂S and for which multiple

isomers In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

are known. The two known isomers with the highest profile in the literature are 1,3,4-oxathiazol-2-one and 1,4,2-oxathiazol-5-one. Oxathiazolone isomers

1,3,4-Oxathiazol-2-one

Molecular and electronic structure

1,3,4-Oxathiaol-2-one derivatives are planar heterocycles that prefer co-planarity with aromatic substituents. It has been proposed that the π system of the ring consists of CNS and CO2 "π islands" that prefer coplanarity to enhance inter-ring π conjugation.

Synthesis

The traditional route for 1,3,4-oxathiazol-2-one synthesis is via 1,3 dipolar cycloaddition, where chlorocarbonylsulfenyl chloride and

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

are heated together in an appropriate

solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...

. Appropriate solvents must dissolve the amide. Typically

toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) at ...

chloroform Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...

is used. A wide variety of amides have been used is the synthesis of 1,3,4-oxathiazol-2-one yielding various derivatives. Variations in this procedure have included doing the reaction under an

inert atmosphere An inert gas is a gas that does not readily undergo chemical reactions with other chemical substances and therefore does not readily form chemical compounds. The noble gases often do not react with many substances and were historically referred to ...

, adding chlorocarbonylsulfenyl chloride drop-wise, and varying the ratio of chlorocarbonylsulfenyl chloride to amide. Variations in procedure may be due to local preferences or

substituent A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...

effects.

Reactions

Decarboxylation leading to isothiazole derivatives

1,3,4-Oxathiazol-2-one

derivatives The derivative of a function is the rate of change of the function's output relative to its input value. Derivative may also refer to: In mathematics and economics * Brzozowski derivative in the theory of formal languages * Formal derivative, an ...

are commonly used in thermal

decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is t ...

reactions to generate the corresponding derivative of the short-lived

nitrile In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix ''cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including met ...

sulfide Sulfide (British English also sulphide) is an inorganic anion of sulfur with the chemical formula S2− or a compound containing one or more S2− ions. Solutions of sulfide salts are corrosive. ''Sulfide'' also refers to chemical compounds lar ...

which may be trapped by 1,3-dipolar cycloaddition reactions to give heterocycles in low to high yields depending on the nature of the

groups.

The intermediate can be trapped with a suitable electron deficient dipolariphile to give stable heterocycles such as

isothiazole An isothiazole, or 1,2-thiazole, is a type of organic compound containing a five-membered aromatic ring that consists of three carbon atoms, one nitrogen atom, and one sulfur atom.''Heterocyclic Chemistry'', 3rd Edition, J.A. Joule, K. Mills, and ...

(seen below). Oxathiazolone decomposition

Other decarboxylation reactions

The intermediate has been successfully trapped using other dipolarophiles including

nitriles In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix ''cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including met ...

alkenes In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...

, and

phosphaalkenes Phosphaalkenes (IUPAC name: alkylidenephosphanes) are organophosphorus compounds with double bonds between carbon and phosphorus(III) with the formula R2C=PR. In the compound phosphorine one carbon atom in benzene is replaced by phosphorus. The re ...

Biologically significant 1,3,40oxathiazol-2-one

Biological significance and applications

Some 1,3,4-oxathiazol-2-one heterocycles have demonstrated selective inhibition of

proteasomes Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by whi ...

in '' Mycobacterum tuberculosis'' and humans. Oxathiazolones HT1171 and GL5 (''right'') selectively inhibited the ''M. tuberculosis'' 26S proteasome and were over 1000-fold less effective on the human proteasome even in high concentrations. Various 5‐styryl‐oxathiazol‐2‐one heterocycles have also been tested as anti-tubercular agents because of their ability to inhibit the ''M. tuberculosis'' 26S proteasome. A

Bortezomib Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is ...

derived 1,3,4-oxathiazol-2-one (bort(L)-oxathiazol-2-one, ''right'') selectively acts against the human proteasome rather than bacterial proteasomes, much like Bortezomib. HT2210 and HT2106 (''right'') were found to have similar effects. Human proteasome inhibition is useful in the treatment of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

neurodegenerative disorders A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

, and

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

References

{{reflist, 30em Oxygen heterocycles Sulfur heterocycles Nitrogen heterocycles

1,3,4-Oxathiazol-2-one

Molecular and electronic structure

Synthesis

Reactions

Decarboxylation leading to isothiazole derivatives

Other decarboxylation reactions

Biological significance and applications

See also

References