Total synthesis, assignment of the absolute stereochemistry, and structure-activity relationship studies of subglutinols A and B.

Journal Article

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 microM). 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.

Full Text

Duke Authors

Cited Authors

  • Kim, H; Baker, JB; Park, Y; Park, H-B; DeArmond, PD; Kim, SH; Fitzgerald, MC; Lee, D-S; Hong, J

Published Date

  • August 2, 2010

Published In

Volume / Issue

  • 5 / 8

Start / End Page

  • 1902 - 1910

PubMed ID

  • 20564278

Electronic International Standard Serial Number (EISSN)

  • 1861-471X

Digital Object Identifier (DOI)

  • 10.1002/asia.201000147

Language

  • eng

Conference Location

  • Germany