12 スクアレン合成酵素阻害物質ザラゴジン酸類の第二世代合成(口頭発表の部)
スポンサーリンク
概要
- 論文の詳細を見る
Zaragozic acids, isolated and characterized independently by Merck and Glaxo in 1992, have attracted considerable synthetic attention because of the biological activity of these compounds and their novel structural aspects. In 1997 we achieved a total synthesis of zaragozic acid C; however, this route suffered from poor selectivity (1.6:1) in the aldol fragment coupling reaction to join the C4-C5 bond. Then, we addressed a second-generation synthesis of zaragozic acids, highlighting an alternative construction of the 2,8-dioxabicyclo[3.2.1]octane core system via a tandem carbonyl ylide formation and 1,3-dipolar cycloaddition process. Toward this end, α-diazo ester 7 was prepared from di-tert-butyl D-tartrate (10) (Scheme 2). After considerable experimentation with respect to a dipolarophile, reaction of 7 and 3-butyn-2-one with catalytic Rh_2(OAc)_4 in refluxing benzene was found to give the desired cycloadduct 22 as a single diastereomer out of the four possible diastereomers in 72% yield (Scheme 3). Dihydroxylation of 22 with OsO_4 followed by sequential benzylation, DIBAL-H reduction, oxidative cleavage of diol with Pb(OAc)_4, and reduction with DIBAL-H/ZnCl_2 effected the installation of the C6, C7 trans diol moiety. Upon protecting group interchange and oxidation, alcohol 26 was uneventfully transformed to the fully functionalized core structure 4. As a means for the elaboration of C1 side chain of 2, we were attracted to the possibility of a cross-metathesis between terminal olefin 32 derived from 4 and allyl acetate 33 (Scheme 4). Gratifyingly, the cross-metathesis reaction with Grubbs' second-generation catalyst (34) in refluxing benzene was found to provide the desired cross-product 35 in good yield. As might be expected from the hindered nature of the olefinic functionality in 32, the dimer 36 from self-metathesis of 32 was not detected. Hydrogenation of 35 followed by debenzylation produced a late intermediate 37 in the synthesis of zaragozic acid C by the Carreira^<8b> and our groups.
- 天然有機化合物討論会の論文
- 2003-09-01
著者
-
橋本 俊一
北大院薬
-
中村 精一
北大院薬
-
平田 勇樹
北大院薬
-
黒崎 貴弘
北大院薬
-
穴田 仁洋
北大院薬
-
橋本 俊一
Fac. Of Pharmaceutical Sciences Hokkaido Univ. Sapporo 060-0812 Jpn
-
中村 精一
Faculty Of Pharmaceutical Sciences Hokkaido University
関連論文
- 30 カルシウムチャネル活性化物質ピンナトキシンAの全合成(口頭発表の部)
- 71(P52) ザラゴジン酸類の合成研究(ポスター発表の部)
- P-74 ピンナトキシンAの全合成研究(ポスター発表の部)
- P-64 含リン脱離基法を用いるO18抗原の合成研究(ポスター発表の部)
- P-45 カルボニルイリドの1,3-双極付加環化反応を機軸とするポリガロリド類の全合成研究(ポスター発表の部)
- ザラゴジン酸の全合成:ロジウム(II)触媒を用いる骨格形成反応 (最新有機合成化学--ヘテロ原子・遷移金属化合物を用いる合成) -- (第3部 天然物合成)
- 奨励賞受賞 中村精一氏の業績
- 12 スクアレン合成酵素阻害物質ザラゴジン酸類の第二世代合成(口頭発表の部)
- 97(P-42) ピンナトキシンAの合成研究(ポスター発表の部)
- 薬学会賞受賞 北 泰行氏の業績
- 金属カルベン中間体を経るイリド形成を機軸とする不斉触媒反応
- ロジウム(II)錯体を用いる不斉触媒反応
- Double Stereodifferentiation in Intramolecular C-H Insertion Reaction toward the Synthesis of 1β-Methylcarbapenem Antibiotics
- ロジウム(II)錯体触媒を用いる不斉C-H挿入反応 (生物活性天然物の合成--複雑な構造をいかにして構築するか) -- (骨格構築法)
- 奨励賞受賞 中島 誠氏の業績
- タキソ-ルと同一の作用機序をもつ抗がん活性抗生物質エポチロンの全合成 (1997年の化学-7-)
- オリゴ糖鎖合成の新戦略
- AN EXTREMELY MILD AND GENERAL METHOD FOR THE CONSTRUCTION OF 1,2-TRANS-β-GLYCOSIDIC LINKAGES VIA GLYCOPYRANOSYL DIETHYL PHOSPHITES WITH PARTICIPATING GROUPS AT C-2
- P-43 16員環マクロリド・ヒグロリド類の全合成研究(ポスター発表の部)
- 含リン脱離基を基盤とする高選択的グリコシル化反応
- プロスタグランジンの合成と医薬 (脂質の化学と生化学) -- (脂質の生化学)
- グリコシル化反応の新展開
- AN EFFICIENT CONSTRUCTION OF 1,2-TRANS-β-GLYCOSIDIC LINKAGES VIA BENZYL-PROTECTED GLYCOPYRANOSYL P, P-DIPHENYL-N-(p-TOLUENESULFONYL)-PHOSPHINIMIDATES
- 現代化学増刊3 有機合成の最前線-高選択性を追及する-, 向山光昭, 土橋源一編, B5判, 252頁, 3800円(東京化学同人)
- 総合有機化学実験 I, II, S.ヒューニッヒ, G.メルクル, J.ザウワー著, 吉村嘉次, 野村祐次郎, 中川淑郎, 橋本弘信訳, A5判/1360頁, II360頁/各2,800円, (森北出版)
- 市販の不斉試薬
- コリスミン酸からプレフェン酸へのClaisen転位はいす型遷移状態を経る
- Catalytic asymmetric synthesis of descurainin via 1,3-dipolar cycloaddition of a carbonyl ylide using Rh2(R-TCPTTL)4
- Enantioselective Construction of a 2,8-Dioxabicyclo[3.2.1]octane Ring System via [2,3]-Sigmatropic Rearrangement of Oxonium Ylide Using Chiral Dirhodium(II) Carboxylates
- Enantioselective amination of silylketene acetals with (N-arylsulfonylimino)phenyliodinanes catalyzed by chiral dirhodium(II) carboxylates: asymmetric synthesis of phenylglycine derivatives
- Catalytic Enantioselective Aziridination of Alkenes Using Chiral Dirhodium(II) Carboxylates
- Dirhodium(II) tetrakis(perfluorobutyrate)-catalyzed 1,4-hydrosilylation of α,β-unsaturated carbonyl compounds
- P-26 CATALYTIC ENANTIOSELECTIVE SYNTHESIS OF (-)-METAZOCINE
- P-16 ENANTIOSELECTIVE SYNTHESIS OF TETRAHYDROPYRAN NATURAL PRODUCTS EXPLOITING DIRHODIUM (II)-CATALYZED HETERO-DIELS-ALDER REACTION
- Asymmetric syntheses of diarylheptanoid natural products (−)-centrolobine and (−)-de-O-methylcentrolobine via hetero-Diels–Alder reaction catalyzed by dirhodium(II) tetrakis[(R)-3-(benzene-fused-phthalimido)-2-piperidinonate]
- Catalytic asymmetric hetero-Diels–Alder route to a key intermediate for the synthesis of calyxin L
- Enantioselective Synthesis of 3-Arylindan-1-ones via Intramolecular C-H Insertion Reactions of α-Diazo-β-Ketoesters Catalyzed by Chiral Dirhodium(II) Carboxylates
- Dirhodium(II) Tetrakis[N-benzene-fused Phthaloyl-(S)-piperidinonate] as a Chiral Lewis Acid: Catalytic Enantioselective Aldol Reactions of Acetate-derived Silylketene Acetals and Aldehydes
- Highly Enantio- and Diastereoselective Construction of 1,2-Disubstituted Cyclopentane Compounds by Dirhodium(II) Tetrakis[N-phthaloyl-(S)-tert-leucinate]-Catalyzed C–H Insertion Reactions of α-Diazo Esters
- Practical Synthesis of Dirhodium (II) Tetrakis[N-phthaloyl-(S)-tert-leucinate]
- A Concise and Enantioselective Synthesis of a C-6 O-Acyl Side Chain Equivalent of Zaragozic Acid A
- Direct and stereoselective synthesis of 2-azido-2-deoxy-β-D-mannosides using the phosphate method
- カルシウムチャネル活性化物質ピンナトキシンAの全合成
- Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C
- Facile and Efficienct Preparation of a C-1 Side Chain Equivalent of Zaragozic Acid C
- Enantioselective Intramolecular C-H Amidation of Sulfamate Esters Catalyzed by Chiral Dirhodium(II) Carboxylates
- An Oscillator-Amplifier Laser System in the 337 nm N_2 Band
- グリコシルジフェニルホスファートを用いる1,2-cis-α-グリコシド結合の立体選択的構築とα-ガラクトシルセラミド(KRN7000)の合成
- 金属カルベン中間体を経るイリド形成を機軸とする不斉触媒反応
- 研究の継続性と独自性
- 学術貢献賞受賞 高畑廣紀氏の業績
- P-67 カルボニルイリドの不斉1,3-双極付加環化反応を機軸とするコプシロシン Aの合成研究(ポスター発表の部)
- P-3 カルボニルイリドの1,3-双極付加環化反応を機軸とするオキサビシクロ骨格を有する天然物の触媒的不斉合成(ポスター発表の部)