25 単一ビシクロ[3.2.1]オクタン型キラル素子による天然物の集約合成 : morphine,yohimbone,vernolepin,ferruginol,calcitriolの新合成(口頭発表の部)

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概要

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• A versatile chiral building block 1 containing a bicyclo[3.2.1]octane framework has been prepared by employing either chemical or enzymatic resolution method. Thus, racemic alcohol (±)-11 used for chemical resolution and racemic acetate (±)-12 used for enzymatic resolution were first prepared from norbornadiene 5 via racemic enone (±)-1. On the asymmetric hydrogen transfer reaction using a chiral diamine-Ru^<II> complex (Ru^<II>-(IS,2S)-TsDPEN), (±)-11 furnished optically enriched (+)-1 (73%ee) and enantiopure alcohol (-)-11, while (±)-12 furnished enantiopure alcohol (+)-11 and enantiopure acetate (-)-12 under hydrolysis conditions in a buffer solution in the presence of Lipase PS. Enantiopure chiral building block 1 could be obtained in both enantiomeric forms from the resolution products thus obtained by employing conventional procedure. Owing to its biased framework, 1 exhibits inherent convex-face selectivity to give rise to a variety of aldol products 2 containing either a cyclohexanone moiety or cyclopentanone moiety by diastereoselective modification of its enone functionality and the secondary oxygen functionality. The aldols 2 carrying a cyclohexanone afford 3,4-substituted cyclohexanones, while the aldols 2 carrying a cyclopentanone afford 2,3-disubstituted cyclopentanones 4 by retro-aldol reaction. On the basis of the inherent stereochemical nature of the chiral building block 1 and the retro-aldol reactivity, diastereocontrolled synthesis of some natural products, 1α,25-dihydroxyvitarnin D3 calcitriol, an antitumor sesquiterpene (+)-vernolepin, a potential indole alkaloid intermediate yohimbone 39, an antibiotic diterpene (+)-ferruginol, and an analgesic alkaloid (-)-morphine, has been investigated. (1) Synthesis of calcitriol-Although the intended convergent synthesis of calcitriol using both enantiomers of the chiral building block 1 has not been accomplished yet, the construction CD-ring moiety 13 starting from (-)-1 has been completed and very close intermediate 20 of the A-ring moiety starting from (+)-1 has been attained. (2) Synthesis of vernolepin-A close intermediate 33 constituting a formal synthesis of (+)-vernolepin has been attained starting from (-)-1 by employing an acid-catalyzed retro-aldol reaction as the key step. (3) Synthesis of yohimbone-Yohimbone 39 has been accomplished in efficient manner involving one-step conversion of 36 into 38 through an acid-catalyzed tandem retro-aldol and intramolecular Pictet-Spengler reaction. (4) Synthesis of ferruginol-A novel and efficient route to (+)-ferruginol has been established using (+)-1 as starting material by discovering a novel tandem acid-catalyzed retro-aldol and oxonium ion-mediated hydrophenanthrene formation reaction. (5) Synthesis of morphine-Based on the tandem rertro-aldol and oxonium ion-mediated hydrophenanthren formation reaction discovered as the key step, a novel and efficient route to (-)-morphine has been developed starting from (-)-1.

• 天然有機化合物討論会の論文
• 2001-09-01

著者

• 小笠原 國郎

  東北大薬

• 長田 宏

  東北大薬

• 宮沢 紀雄

  東北大薬

• 花田 圭介

  東北大薬

• 登坂 綾子

  東北大薬

• Ogasawara Kunio

  Pharmaceutical Institute Tohoku University

関連論文

• 1 シクロヘキサジエノン等価キラル合成素子の創製と天然物合成への活用(口頭発表の部)
• 37 ケトジシクロペンタジエンを活用する生物活性天然物のエナンチオ制御合成(口頭発表の部)
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• 25 単一ビシクロ[3.2.1]オクタン型キラル素子による天然物の集約合成 : morphine,yohimbone,vernolepin,ferruginol,calcitriolの新合成(口頭発表の部)
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• 139(P-94) 全アルドヘキソースの集約的全合成と手法的活用(ポスター発表の部)
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• P-24 1,3-ジオキセビン誘導体の特性を基礎とする天然物の合成(ポスター発表の部)
• Determination of Aconitum alkaloids in blood and urine samples : II. Capillary liquid chromatographic-frit fast atom bombardment mass spectrometric analysis
• PB172 ENANTIO- AND STEREO-CONTROLLED SYNTHESIS OF A VARIETY OF NATURAL PRODUCTS USING COMMON CHIRAL SYNTHON AND KEY REACTION
• A New Route to (+)-Estrone Using a Bicyclo[3.2.1]octane Chiral Building Block(Communications to the Editor)
• A New Synthesis of the Naturally Occurring Free Radical Scavenger Carazostatin
• A New Stereocontrolled Route to(-)-Shikimic Acid

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