Synthetic preparation and evaluation of eeyarestatin (EER1) analogs

ORGN 778

Bidhan A. Shinkre, shinkreb@niddk.nih.gov1, Qiuyan Wang, wangqiu@niddk.nih.gov2, Yihong Ye, yihongy@niddk.nih.gov2, and William C. Trenkle, wtrenkle@niddk.nih.gov1. (1) Chemical Biology Core Facility, National Institutes of Health, NIDDK, 9000 Rockville Pike, Bldg 8, Room 121, Bethesda, MD 20892, (2) Laboratory of Molecular Biology, National Institutes of Health, NIDDK, 9000 Rockville Pike, Bethesda, 20892
Eeyarestatin I (EerI) is a potent anticancer agent currently under investigation at the NIH and has been found to induce inhibition of retro-translocation of proteins which results in preferential cell death of leukemia/lymphoma cancer cells. A general route to EerI analogs was desired to allow a diverse structural library to probe SAR for further biological studies and drug development. A concise method for the preparation of EerI and related molecules sharing the imidazalonone core will be described.