Asymmetric synthesis of bioactive azapyranose derivatives

生物活性氮杂吡喃糖衍生物的不对称合成

• 批准号: 14540491
• 负责人: TAKABE Kunihiko
• 金额: $ 2.3万
• 依托单位: Shizuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14540491/
• 关键词: Azasugar; Enzymatic asymmetric induction; Enzyme inhibition; Alkaloid; Pharmacological activity; Azapyranose; アザピラノース」; 酸素的不斉導入

Azasugar derivatives have been anticipated to be new designed pharmaceuticals which are related to the inhibition of glycosidase.1.Syntheses of isofagomine and paroxetine were investigated. These azasugars potentially have anti-HIV and anti-Alzheimer activities and could be prepared from N-Boc-γ-benzyloxymethyl-α,β-unsaturated-δ-lactam 1, which was produced by chemo-enzymatic process. We achieved the synthesis of isofagomine, however unfortunately, the diastereoselectivity in dihydroxylation of 1 was low. On the other hand, Michael addition of p-fluorophenyl-Grignard reagent to 1 showed high diastereoselectivity and chemical yield. Transformations of Michael adduct gave the chiral paroxetine in good yield.2.Recently we reported the synthesis of a chiral γ-acetoxy-α,β-unsaturated-γ-lactam 2, which was an important chiral building block. The synthesis of (-)-2-epilentiginosine using the chiral lactam 2 was examined. Dihydroxylation of 2, then allylation smoothly proceeded. Transformations of allylation-product gave (-)-2-epilentiginosine, its spectral data was identical with authentic data.

Azasugar衍生物已被研究为新设计的药物，与抑制沙发和帕罗西汀的糖化有关。不幸的是，通过化学酶过程产生的δ-lactam 1良好的产量。我们报道了Lactam 2的合成，这是一个重要的手性构建块。 Alllation产品的转化给出了（ - ）--2-静脉纤维氨酸，其光谱数据与真实数据相同。

项目成果

H.Yoda: "Novel and stereoselective asymmetric synthesis of an amino sugar analogue, furanodictine A."Tetrahedron Letters. 45(8). 1599-1601 (2004)

H.Yoda：“氨基糖类似物呋喃诺克丁 A 的新型立体选择性不对称合成。”四面体快报。

H.Yoda: "Novel and practical asymmetric synthesis of an azetidine alkaloid, penaresidinB."Tetrahedron Letters. 44(5). 977-979 (2003)

H.Yoda：“氮杂环丁烷生物碱 PenaresidinB 的新颖且实用的不对称合成。”四面体快报。

K.Takabe: "Highly regioselective lipase-catalyzed acetylation and hydrolysis of acyclic a, w-acyclic terpenediols"Tetrahedron Letters. 44. 3267-3269 (2003)

K.Takabe：“高度区域选择性脂肪酶催化的无环α、W-无环萜二醇的乙酰化和水解”四面体快报。

K.Takabe: "Preparation of chiral 4-benzyloxymethyldihydrofuran-2-one using lipase-catalyzed kinetic resolution"Bioorganic & Medicinal Chemistry Letters. 12. 2295-2297 (2002)

K.Takabe：“使用脂肪酶催化动力学拆分制备手性 4-苄氧基甲基二氢呋喃-2-酮”Bioorganic

Takabe, K., Hashimoto, H., Sugimoto, H., Nomoto, M., Yoda, H.: "First asymmetric synthesis of the marine furanosesterterpene natural product, (18S)-variabilin employing enzymatic desymmetrization of propanediol derivatives"Tetrahedron : Asymmetry. 15(6).

Takabe, K.、Hashimoto, H.、Sugimoto, H.、Nomoto, M.、Yoda, H.：“利用丙二醇衍生物的酶促去对称化首次不对称合成海洋呋喃酮酯萜烯天然产物 (18S)-variabilin”