8 イミンへの高選択的不斉付加反応を基盤とするイソキノリンアルカロイドの不斉合成(口頭発表の部)
スポンサーリンク
概要
- 論文の詳細を見る
Tetrahydroisoquinoline alkaloid is a class of biologically potent compounds. The existence of 1,2,3,4-tetrahydroisoquinoline (4: TIQ) and 1-methyl-TIQ (6: 1MeTIQ) in the human brain is now in no doubt. The complete prevention of MPTP (1) induced parkinsonism by pretreatment with 6 and inhibition of monoamine oxidase have renewed interest related to the pathogenesis of Parkinson's disease and have been suggested as a leading compound for development of medicine. 1-Phenyl-TIQ (5: 1PhTIQ), originally developed as a general anesthetic agent, also shows phencyclidine-like stereotyped behavior and ataxia. Since the enantiomers were observed to vary in affinity, the synthesis of chiral 1-substituted TIQ is the current focus in medicinal organic chemistry. We report here a novel asymmetric synthetic methodology involving an asymmetric addition of organolithium to an imine and subsequent cyclization by Moffat oxidation as the key steps. In the chiral ligand mediated asymmetric addition of organolithium to imine, a naphthalene unit was developed as a N-substituent of imine to realize high abilities in activation of imine, enantioselectivity, and oxidative dearylation. In the presence of 13, the reaction of methyllithium with the imine (24) bearing N-naphthyl group gave the corresponding amine (25) in up to 97%ee and 99% yield. Conversion of the resulted chiral amine to 1-substituted TIQ was readily achieved through cyclization by Moffat oxidation as a key step. Addition of methyllithium to imine (29) in the presence of 13 gave 30 in 93%ee and 99% yield. Subsequent hydroboration and oxidative work up gave 31 in 76% yield, and following Moffat oxidation afforded TIQ (32) in 75% yield. Dearylation was done by ammonium cerium(IV) nitrate oxidation to give 33 in 94% yield, and finally deacetylation with KOH-hydrazine gave salsolidine (3) in 69% yield. Combination of enantioselective alkylation of imine with the cyclization reaction realized the asymmetric synthesis of potentially biologically active 1-substituted TIQ (3, 6, 7).
- 天然有機化合物討論会の論文
- 1999-09-01
著者
-
富岡 清
京大院薬
-
富岡 清
京都大学大学院薬学研究科
-
長谷川 昌義
京都大学大学院薬学研究科
-
谷山 大典
京大院薬
-
長谷川 昌義
京大院薬
-
Tomioka K
Graduate School Of Pharmaceutical Sciences Kyoto University
関連論文
- 127(P-70) トリコテシノール類の発がんプロモーター活性と合成研究(ポスター発表の部)
- 2-(3-Pyridyl)thiazolidine-4-carboxamide Derivatives. II. Structure-Activity Relationships and Active Configuration of 2-(3-Pyridyl)thiazolidine-4-carboxamides as Platelet-Activating Factor Receptor Antagonists
- 2-(3-Pyridyl)thiazolidine-4-carboxamides. 1. Novel Orally Active Antagonists of Platelet-Activating Factor (PAF)
- 合成医薬品開発の将来と光学活性体
- Stereoselective Reactions. XVI. : Total Synthesis of (-)-β-Bourbonene by Employing Asymmetric (2+2) Photocycloaddition Reaction of Chiral Butenolide
- 21 不斉(2+2)光環化付加反応による抗腫瘍性ジテルペン、スパトールの不斉全合成へのアプローチ
- 薬学会賞受賞寺島孜郎氏の業績
- プロセス化学は21世紀の化学
- REINVESTIGATION ON THE OPTICAL PURITIES OF OPTICALLY ACTIVE TRIMETHYLSILYL ENOL ETHERS OF 4-SUBSTITUTED CYCLOHEXANONES
- 68 不斉酸化反応を用いるアントラサイクリン系抗生物質の短段階不斉合成(口頭発表の部)
- 4酸化オスミウムを用いたオレフィンの不斉酸化反応 (1987年の化学-6-)
- 27 新規発ガンプロモーター、trichothecinol A(口頭発表の部)
- 24 ATPaseドメインを標的とするDNAトポイソメラーゼII阻害剤(口頭発表の部)
- 36 有機リチウムの不斉タンデム型共役付加-閉環反応の開発とLycorine類の不斉全合成への展開(口頭発表の部)
- 医薬品のプロセス化学と触媒
- P-52 エステルエノラートの不斉付加を基盤とするハリクロリンの全合成研究(ポスター発表の部)
- 分子の構造制御と活性化を基盤とした不斉合成反応の開拓と展開 : リチウムで活性化された求核剤の不斉反応
- 分子の構造制御と活性化を基盤とした不斉合成反応の開拓と展開 : リチウムで活性化された求核剤の不斉反応
- 医薬品プロセス化学の産学連携に期待する (特集 プロセス化学の新展開)
- Asymmetric Conjugate Addition of Arylthiols to Enoates and Its Application to Organic Synthesis of Biologically Potent Compounds
- 初夢と矢印
- 105(P-58) ヌクレオシド系酵素阻害剤の作用機序に基づく設計と合成(ポスター発表の部)
- 解説 プロセスケミストリーのめざすもの
- 35 チオラートを開始求核剤とする立体選択的閉環反応を用いたネプラノシンAの全合成(口頭発表の部)
- 学術振興賞受賞 小田嶋和徳氏の業績
- Chiral Ketone-catalyzed Asymmetric Epoxidation of Stilbene with Oxone
- キラル配位子制御による有機リチウム反応剤の不斉付加反応
- Enantioselective Conjugate Addition of Organometallic Reagents to Cycloalkenones by the Aid of Chiral Lactam-Phosphine Ligand
- 8 イミンへの高選択的不斉付加反応を基盤とするイソキノリンアルカロイドの不斉合成(口頭発表の部)
- 有機銅反応剤の不斉共役付加反応
- 有機銅の不斉共役付加反応
- 有機金属反応剤の触媒的不斉共役付加反応 (1996年の化学-1-)
- ASYMMETRIC α-ALKYLATION OF CYCLOHEXANONE BY MEDIATION OF A CHIRAL LIGAND AND THE LEAVING-GROUP EFFECT OF ELECTROPHILES ON ENANTIOSELECTIVITY
- 新しい制がん剤の合成 (1989年の化学-8-)
- 日本薬学会奨励賞受賞青山豊彦氏の業績
- 有機合成化学 : その現代的意義
- 脳と人間
- SYNTHETIC STUDIES TOWARD TRICHOTHECENE SESQUITERPENES. SYNTHESIS OF AN OPTICALLY PURE KEY INTERMEDIATE FOR CALONECTRIN USING HIGHLY STEREOSELECTIVE CYCLIZATION(Communications to the Editor)
- YM-40461 Improves Airway Clearance in Guinea Pigs with Induced Subacute Bronchitis
- YM-40461, a Potent Surfactant Secretagogue, Improves Mucocilliary Clearance in SO_2-Exposed Guinea Pigs
- 2-(3-Pyridyl)thiazolidine-4-carboxamide Derivatives. III. Synthesis of Metabolites and Metabolism of 2-(3-Pyridyl)thiazolidine-4-carboxamides YM461 and YM264 as Platelet-Activating Factor (PAF) Receptor Antagonists
- Stereoselective Reactions. XII. : Synthesis of Antitumor-Active Steganacin Analogs, Picrosteganol and Epipicrosteganol, by Selective Isomerization
- 挑戦する有機化学
- Chiral Ligand-Controlled Asymmetric Conjugate Addition of α-Trimethylsilanylacetate to Acyclic and Cyclic Enones
- A Chiral Ligand-Mediated Asymmetric Addition of a Lithium BHA Ester Enolate to an Aldehyde
- Allylic strain conceptと立体選択的反応のデザイン--キレ-ト形成によらないコンホメ-ションの固定
- エステルエノレ-トの新しい立体選択的アルキル化反応 (1985年の化学-8-)
- Stereoselective Reactions. VIII. Stereochemical Requirement for the Benzylic Oxidation of Lignan Lactone. A Highly Selective Synthesis of the Antitumor Lignan Lactone Steganacin by the Oxidation of Stegane
- Stereoselective Reactions. VII. Synthesis of Racemic and Optically Pure Stegane, Isostegane, Picrostegane, and Isopicrostegane via Highly Selective Isomerization
- Stereoselective Reactions. X. Total Synthesis of Optically Pure Antitumor Lignan, Burseran
- キラルなエナミンを用いる不斉Michael反応 (1988年の化学-8-)
- 有機合成化学の本 : 基礎と進歩
- はじめての学会発表(年会での討論を活発にするには)
- 抗腫瘍活性物質における機能構造相関 (機能構造相関)
- P-67 4級炭素の不斉構築を鍵とする(-)-Aspidospermidineの不斉全合成(ポスター発表の部)