An enantioselective synthesis of the C3–C21 segment of the macrolide immunosuppressive agent FR252921. Issue 26 (29th June 2016)

• Record Type: Journal Article
• Authors: Ghosh, Arun K.; Rodriguez, Samuel
• Is Part Of: Tetrahedron letters. Volume 57:Issue 26(2016)
• Page Start: 2884
• Page End: 2887
• Publication Date: 2016-06-29
• Subjects: FR252921 -- Macrolide -- Synthesis -- Immunosuppressive -- Asymmetric -- Aldol reaction -- Asymmetric reduction; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.05.067
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Synthesis of the C3–C21 segment of the immunosuppressant FR252921 is achieved. The C12 and C13 chiral centers were set by a diastereoselective non-aldol process. Non-aldol route includes, alkylation, oxa-Michael reaction, and ring opening. The C18 stereogenic center was installed using Braun's acetate aldol reaction. Chiral reduction of β-keto-ester with NaBH4 and tartaric acid was investigated. Abstract: 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.