Synthesis of Novel Saccharin Derivatives.
The synthesis of saccharin (1,2-benzisothiazol-3-one-1,1-dioxide) derivatives substituted on the benzene ring has seen limited development despite the longevity of this compound's use as an artificial sweetener. This type of saccharin derivative would however present attractive properties for the development of new bioactive, drug-like small molecule compounds. Here we report the derivatisation of the benzene ring of saccharin using Cu(I)-catalyzed azide alkyne cycloaddition (CuAAC) to synthesise a diverse library of novel saccharin-1,2,3-triazole conjugates. All library compounds retain the capability for interactions with biomolecules via the unmodified sulfonamide and lactam groups of the parent saccharin core heterocycle. The compounds also encompass alternate orientations of the 1,2,3-triazole heterocycle, thus further adding diversity to the potential hydrogen bonding interactions of these compounds with biomolecules of therapeutic interest. Our findings demonstrate that specifically functionalized derivatives of saccharin may be prepared from either saccharin azide or saccharin alkyne building blocks in high yield using CuAAC.
Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111 Australia. rankin.greg13@gmail.com.
Gregory M
GM
Rankin
Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111 Australia. s.poulsen@griffith.edu.au.
Sally-Ann
SA
Poulsen
D002384:Catalysis; D057930:Click Chemistry; D061565:Cycloaddition Reaction; D015394:Molecular Structure; D012439:Saccharin / Q000031:analogs & derivatives*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry
D054852:Small Molecule Libraries; D012439:Saccharin
Cu(I)-catalyzed azide alkyne cycloaddition; click chemistry; glycoconjugate; metal binding group; saccharin; sulfonamide; triazole; zinc binding group