開催日: 2017/09/20 - 2017/09/22
Atropurpuran (1), isolated from Aconitum hemsleyanum, is a unique non-alkaloidal diterpenoid, which possesses an unprecedented cage-like pentacyclic skeleton. Intriguingly, the B-E rings of 1 constitute the highly-symmetrical tetracyclo[5.3.3.04,9.04,12]tridecane skeleton, which includes two bicyclo[2.2.2]octane units. This unusual cage-like structural motif is only found in nature, and there had been no synthetic report of this skeleton before our synthetic study reported in 2011. Herein, we report the total synthesis of 1 based on an intramolecular Diels-Alder reaction of masked ortho-benzoquinone (MOB). The preparation of MOB was commenced from commercially available tetralone 10. The synthetic elaboration including Buchwald-Hartwig reaction, Mukaiyama aldol reaction, and Luche reduction afforded ketone 17. Installation of two alkenes to ketone 17 was successful in a diastereoselective manner. Oxidative dearomatization of phenol gave MOB 20. One-pot intramolecular Diels-Alder/ ring-closing metathesis reaction of MOB 20 afforded pentacyclic compound 22 in 68% yield. Construction of the remaining quaternary carbon center at C4 position was achieved by using aldehyde 28 with t-BuOK and MeI. According to Qin’s total synthesis, 1,2-reduction of ketone 30 completed the total synthesis of 1 in 27 steps from tetralone 10.