102(P-59) (±)-Scopadulinの全合成(ポスター発表の部)  [in Japanese] 102(P-59) The First Total Synthesis of (±)-Scopadulin  [in Japanese]

The first total synthesis of (±)-scopadulin, an antiviral and cytotoxic aphidicolane diterpene isolated from Scoparia dulcis (fam. Scrophulariaceae), is described. Furtheremore, a novel, efficient one-step conversion of primary aliphatic amines into alcohols is also described. The core structure (A/B/C/D ring system) was constructed by an initial synthesis of the B/C/D ring system by our reported methods and a subsequent A ring cyclization by intramolecular aldol condensation. Conjugate cyanation with Et_2AlCN of the C-4 methyl enone occurred highly stereoselectively but unexpectedly from the β-side. So, the cyanation was performed on the C-4 nonsubstituted enone to give stereoselectively a trans-fused A/B ring system with a β-cyanide at C-4. Stereoselective construction of a quaternary carbon at C-4 was achieved by α-alkylation of the cyano group with BOMCl and LDA in high yield. During the conversion of the sterically hindered cyano group to a methyl group, we found a novel reaction for conversion of primary aliphatic amines into alcohols. After several investigations for the reaction conditions, the excess KOH in diethylene glycol at 210℃ under nitrogen atmosphere was found to be the best conditions. The reaction mechanism of this novel reaction will also be discussed. Selective oxidation of the primary alcohol with RuCl_2(PPh_3)_3 in the air followed by Huang-Minion reduction furnished C-4 methyl group efficiently. Finally, the total synthesis of (±)-scopadulin was accomplished by a highly chemo- and stereoselective methylation at C-16, and manipulation of the C-4 α-functionality. The stereoselectivity observed in the MeTi(Oi-Pr)_3-mediated methylation for the generation of a tertiary axial alcohol at C-16 was extremely high.