Daniel Mark Walker

Synthesis of D,L-γ-hydroxyphosphinothricin, a potent new inhibitor of glutamine synthetase

A flexible synthesis of D,L-γ-hydroxyphosphinothricin (GHPPT), a potent inhibitor of the enzyme glutamine synthetase, is described which features silicon-mediated addition of ethyl methylphosphinate to benzyl 2-benzyloxy-carbonylamino-4-oxobutyrate; selective deprotections yield the title compound and various derivatives.

Synthesis of highly substituted 5-(trifluoromethyl)ketoimidazoles using a mixed-solid/solution phase motif.

Using a combination of solid phase synthesis for the preparation of N-substituted-N-acylglycines 7 followed by solution-phase ring transformation of trifluoromethylacyl munchnone intermediate 8, a library of 200 trisubstituted-5-trifluoromethylketo (TFMK) imidazoles 9 was prepared. In a sublibrary, bromoacetate resin 4 was treated with 5 amines in parallel to give N-substituted glycines 5 followed by acylation with 12 acid chlorides to provide, upon cleavage from the resin, 60 individual N-substituted-N-acylglycines 7. The glycines 7 were converted to munchnones 8 by treatment with trifluoroacetic anhydride followed by reaction with benzamidine to give trisubstituted-5-TFMK-imidazoles 9. The structural content of the library was analyzed using PlateView of the LCMS results, and individual members were isolated by automated preparative LCMS.

Preparation of heterocyclic amino acids via intramolecular mukaiyama aldol condensation: Synthesis of a novel cycloleucine analogue

Abstract A novel 5- endo e exo n intramolecular Mukaiyama aldol condensation was employed in a simple synthesis of 3-amino-3-tetrahydrofurancar☐ylic acid, an oxygenated cycloleucine analogue.