Total Syntheses of the Tetracyclic Cyclopiane Diterpenes Conidiogenone, Conidiogenol, and Conidiogenone B

• Published in: Angewandte Chemie International Edition Vol. 55; no. 14; pp. 4456 - 4460
• Main Authors: Hou, Si-Hua, Tu, Yong-Qiang, Wang, Shuang-Hu, Xi, Chao-Chao, Zhang, Fu-Min, Wang, Shao-Hua, Li, Yan-Tao, Liu, Lin
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 24.03.2016
• Subjects: Crystallography, X-Ray; cyclization; Diterpenes - chemical synthesis; Diterpenes - chemistry; Molecular Structure; natural products; semipinacol rearrangement; tetracyclic diterpenes; total synthesis; natural products; semipinacol rearrangement; tetracyclic diterpenes; total synthesis; cyclization
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201600529

Total syntheses of the biologically important and structurally unique tetracyclic diterpenes conidiogenone, conidiogenol, and conidiogenone B of the cyclopiane class are reported. The absolute configuration of naturally occurring conidiogenone B was also corrected. The key step of our strategy involved the highly efficient construction of both ring C and the quaternary carbon center shared by rings A and C through a one‐step regioselective and diastereoselective cycloenlargement in the form of a semipinacol‐type rearrangement. In particular, the desired regioselectivity was made possible by properly adjusting the migratory aptitude of the migrating carbon atom through the introduction of an electron‐donating phenylthio group at this position. Three of a kind: The biologically important tetracyclic diterpenes conidiogenone, conidiogenol, and conidiogenone B (see scheme) were constructed by an efficient strategy involving an intramolecular [2+2] cyclization, a regio‐ and diastereoselective semipinacol rearrangement, and an intramolecular aldol cyclization as key steps. The synthesis also enabled the correction of the absolute configuration of naturally occurring conidiogenone B.