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The Formal Total Synthesis of FR252921 \u2013 An Immunosuppressant<\/p>\n
European Journal of Organic Chemistry Volume 2013, Issue 2, pages 376\u2013388, January 2013 J. S. Yadav and Sandip Sengupta<\/p>\n
Article first published online: 15 NOV 2012 | DOI: 10.1002\/ejoc.201201097<\/p>\n
http:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejoc.201201097\/abstract<\/a><\/p>\n <\/p>\n 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.<\/p>\n Abstract<\/p>\n 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.<\/p>\n <\/p>\n other articles of relevance<\/p>\n Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. kiyotaga-fujine@po.fujisawa.co.jp<\/p>\n<\/div>\n 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 na\u00efve 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.<\/p>\n <\/p>\nFR252921, a novel immunosuppressive agent isolated from Pseudomonas fluorescens no. 408813 II. In vitro property and mode of action.<\/h1>\n
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