Premium
Total Synthesis, Assignment of the Absolute Stereochemistry, and Structure‐Activity Relationship Studies of Subglutinols A and B
Author(s) -
Kim Hyoungsu,
Baker Joseph B.,
Park Yongho,
Park HyungBae,
DeArmond Patrick D.,
Kim Seong Hwan,
Fitzgerald Michael C.,
Lee DongSup,
Hong Jiyong
Publication year - 2010
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201000147
Subject(s) - cytotoxicity , diterpene , pharmacology , stereochemistry , nephrotoxicity , toxicity , acute toxicity , chemistry , drug , medicine , biochemistry , in vitro
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 ( 1 a ) and B ( 1 b ) are diterpene pyrones isolated from Fusarium subglutinans . Compounds 1 a and 1 b are equipotent in the mixed lymphocyte reaction assay and thymocyte proliferation assay (IC 50 =0.1 μ M ). Owing to the lack of toxicity, 1 a and 1 b are expected to be promising new immunosuppressive drugs. Herein, we detail our efforts that have culminated in a stereoselective synthesis of 1 a and 1 b 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 1 a as an immunosuppressive drug with dose‐dependent osteogenic activity.