Asymmetric total synthesis of anti-cancer(+)-discodermolide, directed toward the mass production

抗癌( )-discodermolide不对称全合成，面向量产

• 批准号: 12554022
• 负责人: KIYOOKA Syun-ichi
• 金额: $ 8.51万
• 依托单位: Kyushu University (2002-2003)Kochi University (2000-2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12554022/
• 关键词: Anti-cancer; discodermolide; poly Retide; asymmetric aldol reaction; chiral borane; syn-, anti-propionate; ポリケチド; キラルボラン; シン-,アンチ-プロピオネート; デイスコダーモライド; プロピオネート アルドール

エナンチオならびにジアステレオ高選択的向山アルドール反応と続く高ジアステレオ選択的ラジカル脱ブロム化反応を併用するポリプロピオネート鎖の立体選択的構築する一般的手法が確立された。ポリプロピオネート鎖を含む多様な天然物の合成が可能となった。「Diastereoselective radical debromination approach toward divergent synthesis of syn- and anti-propionate units, coupled with enantioselective and/or diastereoselective Lewis acid-promoted aldol reaction, Tetrahedron : Asymmetry, 14, 2897-2910 (2003)」この手法を用いて、(+)-Discodermolideの大量供給可能な全合成ルートが確立し、天然物とは違った立体化学を持つ骨格合成も検討され、先行するスミスやパターソンらの合成ルートとは違ったユニークな形式全合成が完成した。各段階での選択性はいずれも高く他の系への応用も広く可能である。「Regulated-stereoselective construction of thirteen stereogenic centers necessary for the frame of (+)-discodermolide, based on iterative Lewis acid-promoted aldol reactions, J.Org.Chem.,68,7967-7978 (2003)」

The general method of constructing a three-dimensional lock is established by combining the upward direction of the high-speed selection and the downward direction of the high-speed selection. The synthesis of various natural substances is possible.「Diastereoselective radical debromination approach toward divergent synthesis of syn- and anti-propionate units, coupled with enantioselective and/or diastereoselective Lewis acid-promoted aldol reaction, Tetrahedron : Asymmetry, 14, 2897-2910 (2003)."This technique was used to establish the possibility of total synthesis of (+)-Discodermolide in large quantities, and to complete the synthesis of natural substances by stereochemistry. Each stage of the selection process is high, and each stage of the selection process is high.「Regulated-stereoselective construction of thirteen stereogenic centers necessary for the frame of (+)-discodermolide, based on iterative Lewis acid-promoted aldol reactions, J.Org.Chem., 68,7967-7978 (2003)」

项目成果

S.-i.Kiyooka, K.A.Shahid, F.Goto, M.Okazaki, Y.Shuto: "Regulated-stereoselective construction of thirteen stereogenic centers necessary for the frame of (+)-discodermolide, based on iterative Lewis acid-promoted aldol reactions"J.Org.Chem.. 68. 7967-7978

S.-i.Kiyooka、K.A.Shahid、F.Goto、M.Okazaki、Y.Shuto：“基于迭代路易斯酸促进的羟醛反应，调控 ( )-discodermolide 框架所需的十三个立体中心的立体选择性构建

K.A.Shahid et al.: "A short synthesis of the C15-C21 segment of (+)-discodermolide, based on a ------"Tetrahedron Lett.. 43. 6373-6376 (2002)

K.A.Shahid 等人：“( )-discodermolide 的 C15-C21 片段的简短合成，基于 ------”Tetrahedron Lett.. 43. 6373-6376 (2002)

K.A.Shahid: "A short synthesis of the C15-C21 segment of (+)-discodermolide, based on an asymmetric approach from achiral 2-methyl-1,3-propanediol to versatile enantiopure stereotriads"Tetrahedron Lett.. 43. 6373-6376 (2002)

K.A.Shahid：“( )-discodermolide 的 C15-C21 片段的简短合成，基于从非手性 2-甲基-1,3-丙二醇到多功能对映体纯立体三联体的不对称方法”Tetrahedron Lett.. 43. 6373-6376 (

S.-i.Kiyooka.Y.-N.Li, K.A.Shahid, M.Okazaki, Y.Shuto: "Versatile, high 2,4-syn dialkyl diastereoselection in the radical debromination of α-bromo-α-methyl-δ-valerolactones with tri-butyltin hydride and a catalytic amount of triethylborane"Tetrahedron Lett

S.-i.Kiyooka.Y.-N.Li、K.A.Shahid、M.O​​kazaki、Y.Shuto：“α-溴-α-甲基-δ 自由基脱溴中的多功能、高 2,4-syn 二烷基非对映选择-戊内酯与三丁基氢化锡和催化量的三乙基硼烷“四面体莱特

Kiyooka,S.i. et al.: "Efficient enantio-and diastereoselective synthesis of enantiopure syn-α-bromo-β-hydroxy-α-methyl propionate"Tetrahedron : Asymmetry. 11. 1537-1542 (2000)

Kiyooka, S.i. 等人：“对映体纯顺式-α-溴-β-羟基-α-甲基丙酸酯的高效对映体和非对映选择性合成”四面体：不对称性。