Synthesis of Prostaglandins and Alkaloids using Reactions for Installation of Carbon Chain on the Cyclopentane Ring

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In the past two years (2004, 2005), we have succeeded in synthesis of 2-(5,6-epoxyisoprostane)phosphoryl choline, a new prostanoid, and Δ^<12>-prostaglandin J_2 (Δ^<12>-PGJ_2) starting from the monoacetate of 4-cyclopentene-1,3-diol. Based on these results we have investigated the following researches.(1)Synthesis of tuberonic acid, Δ^2-OPC-8 : 0, and OPC-6 : 0 has been studied. These are metabolites of the linolenic acid cascade in plants. In the synthesis of tuberonic acid, a protective group for the hydroxyl group at the terminal position of the side should be deprotected without isomerization of the cis-orientated two side chains on the cyclopentane ring. We found that THP protective group was removed in the presence of MgBr_2 without the isomerization.(2)Alkenyl reagents which are selectively installed to the monoacetate were applied to cyclohexenyl monoacetate. While the reagents under the original conditions did afford a mixture, the zinc reagents in the presence of TMEDA was found to afford the S^2_N-type product regioselectively over the anti S^2_N' isomer. As an application of this reaction, cannabidiol was successfully synthesized.(3)Propargyl copper reagent derived from the propargyl Grignard reagent and CuCN upon reaction with the monoacetate afforded the S^2_N-type product regioselectively and the product was transformed to the intermediates for synthesis of 2-(5,6-epoxyisoprostane)phosphorylcholine and Δ^<12>-PGJ_2.(4)The S^2_N-type product of the monoacetate with the malonate anion was successfully transformed to the indol and isoquinoline alkaloids.