Asymmetric Total Synthesis of Indole Diterpenes Paspalicine, Paspalinine, and Paspalinine‐13‐ene. Issue 3 (27th November 2021)

• Record Type: Journal Article
• Authors: Guo, Lian‐Dong; Xu, Zejun; Tong, Rongbiao
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-27
• Subjects: Achmatowicz rearrangement -- Indole diterpenes -- Natural products -- Ring-closing metathesis -- Total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202115384
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Paspaline‐derived indole diterpenes (IDTs) are structurally complex mycotoxins with unique tremorgenic activity. Reported are asymmetric total syntheses of three paspaline‐derived IDTs paspalicine, paspalinine and paspalinine‐13‐ene. Our synthesis features a green Achmatowicz rearrangement/bicycloketalization for the efficient construction of FG rings (75 % yield) and a cascade ring‐closing metathesis of dienyne for highly regioselective formation of CD rings (72 % yield). Other highlights include four palladium‐mediated reactions (Stille, aza‐Wacker, Suzuki, and Heck) to forge the BE rings and the installation of two continuous all‐carbon quaternary stereocenters via reductive ring‐opening of cyclopropane and α‐methylation of the conjugate ester. Our new synthetic strategy is expected to be applicable to the chemical synthesis of other paspaline‐derived IDTs and will facilitate the bioactivity studies of these agriculturally and pharmacologically important IDTs. Abstract : The asymmetric total synthesis of three paspaline‐derived indole diterpenes paspalicine, paspalinine and paspalinine‐13‐ene is reported. This synthesis features a green Achmatowicz rearrangement/bicycloketalization for the efficient construction of FG rings, a cascade ring‐closing metathesis of dienyne for highly regioselective formation of CD rings, and four palladium‐mediated reactions to forge BE rings.