Total Synthesis of Sordaricin

• Published in: Journal of organic chemistry Vol. 70; no. 5; pp. 1654 - 1670
• Main Authors: Mander, Lewis N, Thomson, Regan J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.03.2005; Amer Chemical Soc
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Antifungal Agents - chemical synthesis; Chemistry; Chemistry, Organic; Diterpenes; Exact sciences and technology; Molecular Conformation; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Terpenoids; SYNTHASE; REAGENTS; LITHIUM; METABOLITE; DIELS-ALDER REACTION; Intramolecular reaction; Terpenoid; Regioselectivity; Polycyclic compound; High temperature; Aldehyde; Tandem reaction; Total synthesis; Cycloreversion; Antifungal agent; Cycloaddition; Carboxylic acid; Diterpene
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo048199b

An enantioconvergent total synthesis of sordaricin (3), the diterpene aglycon of an important class of antifungal compounds, is described. Two approaches were explored, the first of which utilized a possible biogenetic intramolecular [4 + 2] cycloaddition to form the complete carbon skeleton of the target molecule as a single regioisomer 30. A second approach employed a tandem cycloreversion/intramolecular [4 + 2] cycloaddition process to afford not only the desired product 30 but also significant quantities of the undesired regioisomer iso-30. An investigation into the reasons for the difference in regioselectivity between these two reactions revealed the intervention of a cycloreversion/cycloaddition pathway at elevated temperatures leading to the formation of iso-30. Experimental evidence supports the hypothesis that iso-30 is the more thermodynamically stable of the two regioisomers.