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

酒井 浄 石黒 靖尚 舟越 和久 上野 貢嗣 末宗 洋

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.299-306, 1983-09-15 (Released:2017-08-18)

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Variously functionalized cyclopentanones are important as starting materials for the synthesis of natural products. We have succeeded in a simple, highly stereospecific synthesis of five membered ring ketone using Wilkinson complex. Thus, the precursors, 1-al-4-enes(4a-e,11,13) prepared in optically active form from D-limonene, (+)-limonen-10-ol and 1-carvone in three steps were submitted for RhCl(PPh_3)_3-catalyzed cyclization in CH_2Cl_2 to afford the cis-3,4-disubstituted cyclopentanones(14-22) in good yield (Table 2). The following results were obtained in this cyclization. 1) In all cases, the cis-3,4-disubstituted cyclopentanones were stereospecifically obtained as the sole products. 2) The cyclization reaction of the six membered lactols(12,13) was found to proceed very slowly even if at high temperature. 3) The cis-3,4-disubstituted cyclopentanones obtained in this method were also found to be applicable for the synthesis of bicyclic ketone(23). 4) The configurations of 3,4-disubstituents in each compounds were clarified by the way of chemical correlation and spectral analyses. Further application for the synthesis of ent-cis,cis-dihydro-nepetalactone(39) will be discussed.