A formal synthesis of FR252921, a potent macrocyclic immunosuppressive agent, and a six-step synthesis of vitamin A have been demonstrated. The application of a ruthenium-catalyzed step-economic and environmentally benign strategy for the highly stereo- and chemoselective construction of valuable polyene motifs of FR252921 and vitamin A highlights the syntheses. The key features for the synthesis FR252921 include preparation of the triene moiety followed by two consecutive peptide couplings of the three fragments.

2019-09-04·Journal of the American Chemical Society1区 · 化学

A Domino 10-Step Total Synthesis of FR252921 and Its Analogues, Complex Macrocyclic Immunosuppressants

1区 · 化学

Article

作者: Kubicek, Stefan ; Souris, Caroline ; Coussanes, Guilhem ; Di Mauro, Giovanni ; Kaldre, Dainis ; Aillard, Paul ; Runggatscher, Kathrin ; Chen, Yong ; Maryasin, Boris ; Maulide, Nuno

FR252921, FR252922, and FR256523 are a family of potent macrocyclic polyene immunosuppressive agents with a novel mode of action. However, the lack of an efficient and flexible synthesis has hindered further biological studies, mostly due to the fact that the natural products appear to be kinetic isomers regarding the triene moiety. Herein, we report the development and application of an unprecedented, unique domino Suzuki-Miyaura/4π-electrocyclic ring-opening macrocyclization, resulting in a concise, unified, and stereoselective synthetic route to these complex targets in only 10 steps. This in turn enables ready access to a range of unnatural analogues, among which several compounds showed inhibition of T-lymphocyte proliferation at levels equal or superior to those of the natural products themselves.

2016-06-01·Tetrahedron Letters3区 · 化学

An enantioselective synthesis of the C3–C21 segment of the macrolide immunosuppressive agent FR252921

3区 · 化学

Article

作者: Rodriguez, Samuel ; Ghosh, Arun K

An enantioselective synthesis of the C3-C21 segment of the novel immunosuppressant FR252921 is described. The C12 and C13 stereogenic centers were constructed by a non-aldol process utilizing optically active 4-phenylbutyrolactone. The C18 stereogenic center was installed using Braun's highly diastereoselective acetate aldol reaction. Other key steps involved Curtius rearrangement and Horner-Wadsworth-Emmons olefination reactions.

100 项与 FR-252921 相关的药物交易

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