Asymmetric Synthesis and Molecular Design of Peptidic Renin Inhibitors

肽类肾素抑制剂的不对称合成和分子设计

• 批准号: 05453186
• 负责人: KUNIEDA Takehisa
• 金额: $ 4.67万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05453186/
• 关键词: 2-Amino alcohol; 2-Oxazolone; 2-Oxazolidinone; Asymmetric synthesis; Chiral auxiliary; Hydroxy amino acid; Asymmetric reduction; Chiral Synthesis; アルドール反応

1.Development of Novel Chiral Synthons for Unusual Amino AcidsIntramolecular radical cyclizations of 2,2-dichloroacyl groups to the olefinic moiety of 2-oxazolone followed by dechlorination with (Me_3) _3SiH furnished an excellent route for the stereoselective preparation of 2-aminoalcohol chiral synthons with three ajacent asymmetric centers.2.Chiral Synthesis of Hydroxyamino Acids of Biological SignificanceDiastereoselective aldol reactions between alpha-amino aldehydes and N-acetyl derivatives of the chiral 2-oxazolidinones previously developed as chiral auxiliaries resultedin stereoselective formation of gamma-amino-beta-hydroxy acids which served as the compornents essential for the renin inhibitory peptides.3.Higly Efficient Catalytic Reductions of KetonesAsymmetric reduction of ketones with BH_3 proceeded with catalytic amount of the 2-aminoalcohol derived from the newly developed 2-oxazolidinone, HMCOx, to give the enantiomerically pure secondary alcohols.

1.新型特殊氨基酸手性合成子的开发2,2-二氯酰基分子内自由基环化为2-恶唑酮的烯基部分，然后用(Me_3)_3SiH脱氯，为2-氨基醇手性合成子的立体选择性制备提供了良好的途径具有三个相邻的不对称中心。2.羟基氨基的手性合成具有生物学意义的酸先前作为手性助剂开发的手性2-恶唑烷酮的α-氨基醛和N-乙酰基衍生物之间的非对映选择性羟醛反应导致立体选择性形成γ-氨基-β-羟基酸，其作为肾素抑制肽的必需成分.3.酮的高效催化还原用BH_3进行酮的不对称还原催化量的衍生自新开发的 2-恶唑烷酮 HMCOx 的 2-氨基醇，得到对映体纯的仲醇。

项目成果

石塚 忠男: "高性能2-オキサゾリジノン系不斉補助剤の開発" 有機合成化学協会誌. 53. 95-103 (1995)

Tadao Ishizuka：“高性能 2-恶唑烷酮基手性助剂的开发”有机合成化学学会杂志 53. 95-103 (1995)。

Keiko Otsuka: "Sterically Congested Chiral N-Acetyl 2-Oxazolidinone as Acetyl Enolate Equivalents in Stereoselective Aldol Reactions" Chem.Pharm.Bull.748-750 (1994)

Keiko Otsuka：“空间拥挤的手性 N-乙酰基 2-恶唑烷酮作为立体选择性羟醛反应中的乙酰烯醇化物等价物”Chem.Pharm.Bull.748-750 (1994)

Noriaki Hashimoto: "Highy Efficient Chiral 2-Oxazolidinone Auxiliaries Derived from Methyl-cyclopentadienes and 2-Oxazolone." Tetrahedron Letters. 35. 721-724 (1994)

Noriaki Hashimoto：“源自甲基环戊二烯和 2-恶唑酮的高效手性 2-恶唑烷酮助剂。”

Tadao Ishizuka: "Extremely Powerful Chiral 2-Oxazolidinone Auxiliaries" J.Syn.Org.Chem.53. 95-103 (1995)

Tadao Ishizuka：“极其强大的手性 2-恶唑烷酮助剂”J.Syn.Org.Chem.53。

石塚忠男: "高性能2-オキサゾリジノン系不斉補助剤の開発" 有機合成化学協会誌. 53. 95-103 (1995)

Tadao Ishizuka：“高性能 2-恶唑烷酮基手性助剂的开发”有机合成化学学会杂志 53. 95-103 (1995)。