42 新Indole閉環法を利用した6,7-Secoagroclavineの全合成

抄録

6,7-Secoagroclavine (3), an ergot alkaloid isolated from Claviceps purpurea, strain AA-218, was first synthesized from 1-methoxycarbonylpyrrole (1). Endoperoxide (4) of 1 was reacted with 1-trimethylsilyloxy-1,3-butadiene in the presence of SnCl_2 and 4-(1-methoxycarbonyl-2-pyrrolyl) crotonaldehyde (6) thus obtained was treated with the Grignard reagent derived from 2-methyl-2-bromoethyl-1,3-dioxolane, followed by oxidation with pyridinium chlorochromate to produce 7. SnCl_4 catalyzed cyclization of 7 afforded 1-methoxycarbonyl-4-(3-oxo-1-butyl) indole (2) in 52% yield, accompanied by concomitant hydrolysis of the dioxolane group. 2 was transformed to 21 by way of 19 and 20, and the formylation of 21 with the Vilsmeier-Haack reagent, followed by alkali treatment produced a tricyclic indole derivative 22, which was reduced with LiAlH_4 in THF. Successive treatment of the reduction mixture with i) ClCOOMe, Et_3N in CH_2Cl_2, ii) LiAlH_4 in THF, and iii) ClCOOCH_2Ph, Et_3N in CH_2Cl_2, afforded 23d and 24d in 27% and 33% yields, respectively. After removal of the ethylene ketal group from 23d, 25d=35 was treated with MeMgI, followed by dehydration with p-TsOH in boiling benzene gave 40, whose protecting group on the nitrogen was cleaved with Na in liquid NH_3 to complete the total synthesis of ±-3.