1130279-41-2Relevant academic research and scientific papers
Total synthesis, assignment of the absolute stereochemistry, and structure-activity relationship studies of subglutinols A and B
Kim, Hyoungsu,Baker, Joseph B.,Park, Yongho,Park, Hyung-Bae,DeArmond, Patrick D.,Kim, Seong Hwan,Fitzgerald, Michael C.,Lee, Dong-Sup,Hong, Jiyong
, p. 1902 - 1910 (2011/04/15)
Immunosuppressive drugs are used to prevent rejection of transplanted organs and treat autoimmune diseases. Clinically approved immunosuppressive drugs possess undesirable side effects, including acute neurological toxicity, chronic nephrotoxicity, and osteoporosis. As a result, considerable efforts have been devoted to the identification of immunosuppressive natural products that lack cytotoxicity and undesirable side effects on bone structure. Subglutinols A (1a) and B (1b) are diterpene pyrones isolated from Fusarium subglutinans. Compounds 1a and 1b are equipotent in the mixed lymphocyte reaction assay and thymocyte proliferation assay (IC50=0.1 μm). Owing to the lack of toxicity, 1a and 1b are expected to be promising new immunosuppressive drugs. Herein, we detail our efforts that have culminated in a stereoselective synthesis of 1a and 1b from the (S)-(+)-5-methyl-Wieland-Miescher ketone and determined their absolute stereochemistries. We also present initial biological data to show the great potential of 1a as an immunosuppressive drug with dose-dependent osteogenic activity.
