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)
スポンサーリンク
概要
- 論文の詳細を見る
(-)-Neplanocin A is a carbonucleoside isolated from Ampullariella regularis in 1981, and have a S-adenosylhomocystein hydrolase inhibitory activity. Until today, several examples of the total synthesis were reported. However, there is no precedent of the total synthesis using intra-molecular aldol reaction for ring construction of neplanocin A. During the course of our studies on development of asymmetric reaction, we have already developed a lithium thiolate-catalyzed stereoselective Michael-aldol tandem reaction of α,β-unsaturated esters with aldehydes. We describe here a development of lithium thiolate-initiated Michael-aldol tandem cyclization reaction as an extension of intermolecular tandem reaction, and a total synthesis of (-)-neplanocin A by using the present cyclization as a key reaction for construction of five-membered ring. The reaction of ω-oxo-α,β-unsaturated ester 6 with 0.2 equiv of lithium thiophenolate (PhSLi) in the presence of 2 equiv of phenyl trimethylsilyl sulfide (PhSTMS) in THF at 0℃ for 2h gave cyclization products 7a and 7b in 61% and 18% yields, respectively. The presence of PhSTMS, which traps lithium alkoxide as a stable TMS ether, was essential for both high yield and stereoselectivity. High yield and stereoselectivity was also obtained by using lithium benzylthiolate (BnSLi) as a nucleophile which has higher nucleophilicity than that of PhSLi. The reaction of 6 with 1.2 equiv of BnSLi in THF at -20℃ proceeded within 1h to give cyclization product 11 in 95% yield as a sole product. We applied this cyclization reaction to total synthesis of (-)-neplanocin A. TBS-protected chiral ω-oxo-α,β-unsaturated ester 23, which was derived from D-mannitol, was treated with 1.2 equiv of BnSLi in THF at-20℃ for 0.5 h to give three separable cyclization products 24a, 24b and 25 in 34%, 28% and 11% yields, respectively. After conversions of protective groups, the benzylsulfanyl part of 29 was removed by oxidation to sulfoxide and subsequent thermal elimination. Through the functional group transformations of 30, we have achieved a total synthesis of (-)-neolanocin A.
- 2001-09-01
著者
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)
- 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
- 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)