著者

鈴木 正昭 柳沢 章 野依 良治

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 26 (ISSN:24331856)

巻号頁・発行日

pp.569-576, 1983-09-15 (Released:2017-08-18)

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The tandem organocopper conjugate addition with α,β-unsaturated ketones/aldehyde trapping of the enolate intermediates provides an efficient way of vicinal carba-condensation. Methyl esters of prostaglandin (PG) D_1, D_2, and I_2 haveb been synthesized on the basis of this strategy. Combination of (R)-4-t-butyldimethylsiloxy-2-cyclopentenone, an organocopper reagent derived from (S,E)-1-iodo-3-tetrahydropyranyloxy-1-octene, and 6-methoxycarbonylhexanal leads in one step to a PG skeleton, 7-hydroxy-11-O-t-butyldimethylsilyl-15-O-tetrahydropyranyl-PGE_1 methyl ester. Dehydration, giving a Δ^7-PGE_1 derivative, followed by tributyltin hydride reduction affords 11-O-t-butyldimethylsilyl-5-O-tetrahydropyranyl-PGE_1 methyl ester. Stereoselective reduction of the 9-keto group, leading to the 9α alcohol, tetrahydropyranyl protection of the hydroxyl function, and desilylation give 9,15-O-bis(tetrahydropyranyl)PGF_<2α> methyl ester. Jones oxidation of the 11-hydroxyl group and removal of the tetrahydropyranyl protective groups completes the synthesis of (+)-PGD_1 methyl ester. The three-component coupling process using 6-carbomethoxy-2-hexynal as α sidechain unit gives 5,6-dehydro-11-O-t-butyldimethylsilyl-15-O-t-tetrahydropyranyl-PGE_2 methyl ester. Stereoselective conversion of the 9-keto group to 9α hydroxyl, removal of the 7-hydroxyl by the Barton's procedure, and partial hydrogenation of the 5,6-triple bond over Lindlar catalyst produce 11-O-t-butyldimethylsilyl-15-O-tetrahydropyranyl-PGF_<2α> methyl ester. (+)-PGD_2 methyl ester is obtainable from this intermediate by the procedure as described above. 5,6-Dehydro-11-O-bis(t-butyldimethylsilyl)PGF_<2α> methyl ester is obtained in four steps from (R)-4-t-butyldimethylsiloxy-2-cyclopentenone via the three-component coupling process. Intramolecular alkoxymercuration of the acetylenic alcohol, followed by reductive demercuration and desilylation has realized a short synthesis of (+)-PGI_2 methyl ester.

著者

中川 威雄 柳沢 章 鈴木 清

出版者

The Society of Fiber Science and Technology, Japan

雑誌

繊維学会誌 (ISSN:00379875)

巻号頁・発行日

vol.39, no.4, pp.P121-P127, 1983-04-10 (Released:2008-11-28)

参考文献数

14