The oxathiazolones are a family of heterocyclic compounds in which the parent derivative has the molecular formula C2HNO2S and for which multiple Isomer are known. The two known isomers with the highest profile in the literature are 1,3,4-oxathiazol-2-one[, and references therein.]
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 CO
2 "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 are heated together in an appropriate
solvent.
Appropriate solvents must dissolve the amide. Typically
toluene or
chloroform 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, 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 effects.
Reactions
Decarboxylation leading to isothiazole derivatives
1,3,4-Oxathiazol-2-one derivatives are commonly used in thermal
decarboxylation reactions to generate the corresponding derivative of the short-lived
nitrile sulfide which may be trapped by 1,3-dipolar cycloaddition reactions to give heterocycles in low to high yields depending on the nature of the
substituent groups.
[[File:Oxathiazole13dipolegeneric.jpg|center|
]]The intermediate can be trapped with a suitable electron deficient dipolariphile to give stable heterocycles such as isothiazole (seen below).
Other decarboxylation reactions
The intermediate has been successfully trapped using other dipolarophiles including
Nitrile,
Alkene, and
Phosphaalkene.
Biological significance and applications
Some 1,3,4-oxathiazol-2-one heterocycles have demonstrated selective inhibition of
Proteasome 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 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.
See also
