Development of practical synthetic method for preparation of alcohols in chiral from.

开发用于制备手性醇的实用合成方法。

• 批准号: 05650871
• 负责人: SATO Fumie
• 金额: $ 1.34万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 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-05650871/
• 关键词: Asymmetric Synthesis; Asymmetric epoxidation; Asymmetric dihydroxylation; Allyl Alcohol; Butyrolactone; Chiral building block; Hydromagnesiation Reaction; Allylsilane; 酸化; アルコール; フリルアルコール; ブテノライド; ヒドロマグネシウム化; シリル化合物; 不斉酸化反応; グリニャール反応剤; フラン

If biologically active compounds have asymmetric center, the two enantiomers, usually, show differnent biological activities. Thus it has been required to develop one enantiomer, not racemic compound, as drugs or agricalutural chemicals. The development of practical method which can be viable in indurially scale production, therefore, has been the important subject in organic synthesis. The purpose of the present research is the development of efficient and practical method for synthesis of alcohols in optically pure from. Since alcohols are embeded in various kinds of biologically active substances and also have been widely accepted as useful intermediates for synthesis of natural compounds, the practical synthetic methodolgy for preparation of optically active alcohols has been strongly anticipated.The Sharpless asymmetric dihydroxylation of allyl silane followed by the Petterson reaction provided optically active allyl alcohols in excellent yields. The Sharpless asymmetric dihydroxylation of enyne gave propargylic alcohols having another hydroxyl group at beta-position. Hydromagnesiation of these diols followed by treatment with aldehyde or CO_2 provided furyl alcohols or butenolides, respectively, in a chiral form. By using these chiral alcohols as chiral building block, a few biological compounds were synthesized.

如果具有生物活性的化合物具有不对称中心，则两种对映体通常表现出不同的生物活性。因此，需要开发一种对映体，而不是外消旋化合物作为药物或农用化学品。因此，开发实用的工业化生产方法已成为有机合成研究的重要课题。本研究的目的是发展一种高效、实用的光学纯醇的合成方法。由于醇类化合物广泛存在于各种生物活性物质中，同时也是合成天然化合物的重要中间体，因此人们对制备光学活性醇类化合物的实用合成方法有着强烈的期待，烯丙基硅烷的Sharpless不对称二羟基化反应和Petterson反应是制备光学活性烯丙基醇类化合物的高产率方法。烯炔的Sharpless不对称二羟基化反应得到了β位上又多了一个羟基的炔丙醇。这些二元醇经氢镁化、醛或CO_2处理后分别得到手性呋喃醇或丁烯内酯。利用这些手性醇作为手性结构单元，合成了一些生物活性化合物。

项目成果

Yasushi Miyazaki: "Synthesis of β-Hydroxy-γ-trimethylsilyl-γ-butyrolactone as Key Chiral Building Block for Preparation of Four-Carbon Chain Units Having Tertiary Stereogenic Carbon" Tetrahedron Letters. 35-25. 4389-4392 (1994)

Yasushi Miyazaki：“作为制备具有叔立构碳的四碳链单元的关键手性构件的 β-羟基-γ-三甲基甲硅烷基-γ-丁内酯的合成”四面体快报 35-25 (1994)。

Kousuke Tani: "Synthesis of Optically Active Furfuryl Alcohols and Butenolides from trans- 1-Trimethysilyl-3-alken-1-ynes via Successive Asymmetric Dihydroxylation and Hydromagnesiation Reactions" Tetrahedron Letters. 34-31. 4975-4978 (1993)

Kousuke Tani：“通过连续不对称二羟基化和水镁化反应从反式 1-三甲基甲硅烷基-3-烯-1-炔合成光学活性糠醇和丁烯内酯”四面体快报。

Hirodazu, Urabe: ""Diastereoselective Addition of Nucleophiles to Carbonyl Compounds and Imines Controlled by alpha, beta-Epoxy Group and Its Application in Organic Synthesis."" Journal of Synthetic Organic Chemistry. 51-1. 32-42 (1993)

Hirodazu，Urabe：““亲核试剂与α，β-环氧基控制的羰基化合物和亚胺的非对映选择性加成及其在有机合成中的应用。”合成有机化学杂志。

Yasushi Miyazaki: "Synthesis of β-Hydroxy-γ-trimethylsilyl-γ-butyrolactone as Key Chiral Building Block for Preparation of Four-Carbon Chain Units Having Tertiary Stereogenic Carbon" Tetrachedron Letters. 35-25. 4389-4392 (1994)

Yasushi Miyazaki：“β-羟基-γ-三甲基甲硅烷基-γ-丁内酯作为制备具有叔立构碳的四碳链单元的关键手性构件的合成”Tetrachedron Letters 35-25 (1994)。

占部 弘和: "α、β-エポキシ基により制御されたカルボニル化合物およびイミン類への求核試剤のジアステレオ選択的付加反応とその応用" 有機合成化学協会誌. 51-1. 32-42 (1993)

Hirokazu Urabe：“由 α,β-环氧基控制的亲核试剂与羰基化合物和亚胺的非对映选择性加成反应及其应用”有机合成化学学会杂志 51-1（1993）。