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Solid-phase synthesis of an oxalic acid amide library.
Taxiarchis M Georgiadis1, Nand Baindur, Mark R Player
13-Dimensional Pharmaceuticals, Inc., 8 Clarke Drive, Cranbury, NJ 08512, USA.
Journal of Combinatorial Chemistry
|March 9, 2004
Summary
Researchers developed a new method using oxalic acid to create enzyme inhibitors. This technique efficiently synthesizes phosphate biosteres, which are valuable for drug discovery and medicinal chemistry.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Biochemistry
Background:
- Monoamides of oxalic acid are explored as bioisosteric replacements for phosphate groups.
- Phosphate groups are crucial in enzyme active sites and biological processes.
Purpose of the Study:
- To demonstrate the use of oxalic acid as a linker for solid-phase synthesis of phosphate biosteres.
- To develop a rapid method for synthesizing libraries of N-aryloxamic acids and 2-(oxalylamino)benzoic acids (OBAs).
Main Methods:
- Utilizing oxalic acid linked to Wang resin to form resin-bound acid chlorides.
- Reacting resin-bound acid chlorides with arylamines to form N-aryloxamic acids.
- Cleaving the final products from the resin using trifluoroacetic acid.
Main Results:
- Successful synthesis of individual or libraries of phosphate biosteres.
- Efficient preparation of resin-bound N-aryloxamic acids (oxanilic acids).
- Good yields of 2-(oxalylamino)benzoic acids (OBAs) after cleavage, without intermediate purification.
Conclusions:
- The described solid-phase method provides a rapid and efficient route to phosphate biosteres.
- This approach is advantageous for combinatorial chemistry and the discovery of new enzyme inhibitors.
- Elimination of purification steps enhances the utility of this synthetic strategy.