The Formal Total Synthesis of FR252921 – An Immunosuppressant European Journal of Organic Chemistry Volume 2013, Issue 2, pages 376–388, January 2013
J. S. Yadav and Sandip Sengupta Article first published online: 15 NOV 2012 | DOI: 10.1002/ejoc.201201097 http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201201097/abstract
The formal total synthesis of FR252921 is described. The key steps include the preparation of three fragments starting from 1,4-butanediol, (R)-malic acid, and prenol, respectively, followed by
two consecutive peptide couplings of the three fragments. Abstract The formal total synthesis of FR252921 is described. The key steps include the preparation of three fragments starting from 1,4-butanediol, (R)-malic acid, and
prenol, respectively, followed by two consecutive peptide couplings of the three fragments. Other key steps involve an allene-type rearrangement or enyne isomerization to install the triene
moiety, a Seebach methylation, a Julia olefination to construct the trisubstituted diene unit, and an enzymatic resolution strategy to generate the C-18 stereocenter. other articles of relevance
FR252921, a novel immunosuppressive agent isolated from Pseudomonas fluorescens no. 408813 II. In vitro property and mode of action.
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. email@example.com
A novel immunosuppressive agent, FR252921 was isolated from the cultured broth of a species of Pseudomonas fluorescens. We have shown that FR252921 inhibited splenic proliferation stimulated with
LPS, insensitive to calcinuerin inhibitor. In this study, FR252921 was found to inhibit IL-2 and IL-12 production as well as proliferaion of splenocyte. Analysis of transcription activity
revealed that FR252921 inhibited activating protein-1 (AP-1). Exposures of antigen presenting cells (APC) to FR252921 attenuated proliferation supplemented by naïve T cells. Further, FR252921
strongly suppressed splenic dendritic cell proliferation stimulated with LPS and anti-CD40 mAb, while it did not inhibit purified T cell activation, including CD154 expression and IL-2
production. These results suggest that APC is dominant target cell population.
2009;15(14):3457-73. doi: 10.1002/chem.200802649.
Synthesis of two bioactive natural products: FR252921 and pseudotrienic acid B.
Amans D, Bellosta V, Cossy J.
Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS, 10 rue Vauquelin, 75231 Paris, France.
Concise and highly convergent syntheses of the immunosuppressive agent FR252921 and the related antimicrobial natural product pseudotrienic acid B were achieved from a common intermediate by
using optically active titanium complexes to control the configuration of the stereogenic centers, a highly stereo- and regioselective cross-metathesis to generate the triene moieties, and a
Stille cross-coupling to install the dienic units.
Synthesis of a Promising Immunosuppressant: FR252921
Laboratoire de Chimie Organique, ESPCI, CNRS, 10 rue Vauquelin, 75231 Paris Cedex 05, France
Org. Lett., 2007, 9 (23), pp 4761–4764