Novel stereoselective synthesis of α-methylene-β-substituted pyroglutamates, and α-alkylidene-pyroglutamates has been achieved via substrate controlled asymmetric alkylation of l-threonine derived oxazole with Baylis-Hillman reaction based allyl bromides and acetates, respectively. The synthesized compounds were evaluated for their proteasome inhibition and cytotoxicity on multiple myeloma cells.
Bibliographical noteFunding Information:
We thank the Departments of Chemistry and Biochemistry, University of Minnesota Duluth and Rowan University for the funding. Partial support for this work was also provided by research grants from the University of Minnesota Academic Health Center Faculty Development Grant (V.R.M.), Whiteside Institute for Clinical Research (V.R.M.), and Rowan University Non-Salary Financial Support Grants (NSFSG) (S.C.J.). We thank Dr. Victor G. Young, Jr. (University of Minnesota X-ray Crystallographic Laboratory) for providing the crystal structure.
- Baylis-Hillman bromides/acetates
- Pyroglutamates (γ-carboxy-γ-lactams)
- Substrate controlled alkylation