UK-1 analogues: methods of preparation and use
View Patent ↗The present invention includes a number of structural analogues of UK-1. A comparision of the anticancer activity of the UK-1 analogues with their ability to inhibit the growth of methicillin-sensitive and methicillin-resistant Staphylococcus aureus demonstrates that a structurally simplified analogue of UK-1 retains the natural product's selective activity against cancer cells. Structurally conservative changes to UK-1 that diminish Mg 2+ -binding ability may result in a dramatic decrease in cancer cell cytotoxicity. The results may establish a minimum structural pharmacophore as well as a functional role for Mg 2+ -binding in the selective cytotoxicity of UK-1.
1. A method of synthesizing a chemical compound comprising a cyclic ring having the structure II
where R 1 is alkyl or aryl;
where each R 2 is independently hydrogen, alkyl, aryl, or halogen;
where n is 1 to 4; and
where X is N and Y is O, comprising:
reacting an acyclic compound haying the structure III with an acid in a hydrocarbon solvent;
where R 1 and R 2 are independently hydrogen, alkyl, aryl, or halogen;
where n is 1 to 4; and
where X and Y are independently N or O; heating the reaction.
2. The method of claim 1 , wherein the acid is an organic acid.
3. The method of claim 1 , wherein the acid is p-TsOH.
4. The method of claim 1 , wherein the solvent is an organic solvent.
5. The method of claim 1 , wherein heating the reaction comprises a temperature above 80° C.
6. The method of claim 1 , further comprising cooling the reaction down to at least room temperature and filtering off the acid.