Development of Novel Chiral Synthons for 2-Amino Alcohols of Biological Interest.

具有生物价值的 2-氨基醇的新型手性合成子的开发。

• 批准号: 03453157
• 负责人: KUNIEDA Takehisa
• 金额: $ 4.93万
• 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: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03453157/
• 关键词: 2-Amino alchol; 2-Oxazolone; 2-Oxazolidinone; Asymmetric synthesis; Chiral auxiliary; Statine; Condensing reagent; Chiral Synthesis; 2ーオキサゾロン; 2ーオキサゾリドン; チオリン酸

1. Vesatile Chiral Synthons : Using the 2-exo-alkoxy-apocamphanecarboxylic acid derivatives as chiral auxiliaries, 2-oxazolone was enantioselectively functionalized to the reactive intermediates (synthons) by means of methoxybromination, methoxyselenylation and [4+2]cycloaddition reactions. Stepwise and stereospecific conversions of the synthons, thus obtained with excellent diastereoselectivity, provided facile routes for the preparation of enantiomerically pure 2-amino alcohols.2. Syntheses of 2-Amino Alcohols of Biological Interest : The synthons, described as above, were effectively converted to bioactive amino-hydroxycarboxylic acids alcohols such as statine and its analogues, 3-amino-2-hydroxy-4-phenylbutanoic acid (component of bestatine), and 3-amino-2-hydroxy-5-methylhexanoic acid (component of amastatin), in optically pure forms as well as dihydrosphingosine.3. New Chiral Auxiliaries : Chiral 2-oxazolidinones featured by bicyclo [2.2.2] octane ring system (DHAOx and DMAOx) were synthesized and successfully utilized as highly efficient auxiliaries in the Diels-Alder reactions, alkylations, aldol reactions and the Michael reactoins. Both enentiomers of the 2-amino alcohols, readily obtained by ring opening of the above DHAOx and DMAOx, served as excellent and unique catalysts in enantioselective alkylations of aldehydes with dialkylzinc.4. Highly Reactive Condensing Reagents : Thiophosphoryl derivatives activated by 2-oxazolone were developed as powerful and stable condensing reagents for the synthesis of amides including peptides and beta-lactams, esters and thioesters.

1. 多功能手性合成子：以2-外型烷氧基阿莰烷甲酸衍生物为手性助剂，通过甲氧基溴化、甲氧基硒化和[4+2]环加成反应将2-恶唑酮对映选择性官能化为反应性中间体（合成子）。合成子的逐步立体定向转化，具有优异的非对映选择性，为制备对映体纯的2-氨基醇提供了简便的途径。2．具有生物价值的2-氨基醇的合成：如上所述，合成子被有效地转化为生物活性氨基-羟基羧酸醇，例如他汀及其类似物，3-氨基-2-羟基-4-苯基丁酸（贝他汀的成分） ）和3-氨基-2-羟基-5-甲基己酸（amastatin的成分），光学纯形式以及二氢鞘氨醇。3。新型手性助剂：合成了双环[2.2.2]辛烷环系统（DHAOx和DMAOx）的手性2-恶唑烷酮，并成功用作Diels-Alder反应、烷基化、羟醛反应和Michael反应中的高效助剂。 2-氨基醇的两种对映异构体很容易通过上述DHAOx和DMAOx开环获得，在醛与二烷基锌的对映选择性烷基化中充当优异且独特的催化剂。4．高反应性缩合试剂：由 2-恶唑酮活化的硫代磷酰基衍生物被开发为强大且稳定的缩合试剂，用于合成酰胺（包括肽和 β-内酰胺）、酯和硫酯。

项目成果

Hirofumi Matsunaga: "CONFORMATIONALLY RIGID CHIRAL [4+2]CYCLOADDUCTーBASED 2ーOXAZOLIDINONS AS NEW AUXILIARIES" Tetrahedron Lett.32. 7715-7718 (1991)

Hirofumi Matsunaga：“构象刚性手性 [4+2]CYCLOADDUCT－基于 2－恶唑烷酮作为新的助剂”Tetrahedron Lett.32 (1991)。

Seigo Ishibuchi: "Facile Synthesis of (2S,3R)-3-Amino-2-hydroxy-carboxylic Acids, The Key Components of Amastatine and Bestatine." Natural Product Lett.1. 21-24 (1992)

Seigo Ishibuchi：“轻松合成 (2S,3R)-3-氨基-2-羟基-羧酸，这是金刚烷胺和贝斯塔汀的关键成分。”

Seigo Ishibuchi: "LEWIS ACIDーPROMOTED DIRECT SUBSTITUTION OF 4ーMETHOXYーAND 4ーPHENYLTHIOー2ーOXAZOLIDINONES BY ALKYLCUPRATES.FACILE PREPARATION OF(3S,4S)ーSTATINE AND(3S,4S)ーCYCLOHEXYLSTATINE." Tetrahedron Lett.32. 3523-3526 (1991)

Seigo Ishibuchi：“刘易斯酸 - 促进烷基铜酸酯直接取代 4 - 甲氧基 - 和 4 - 苯基硫代 - 2 - 恶唑烷酮。(3S,4S) - 斯达汀和 (3S,4S) - 环己基斯达汀的简便制备。”32 .3523-3526 (1991)

Teruyuki Otsubo: "New Condensing Reagents: Thiophosphorus Compounds Activated by 2-Oxazolone and 2-Benzoxazolinone Heterocycles." HETEROCYCLES. 33. 131-134 (1992)

Teruyuki Otsubo：“新型缩合试剂：由 2-恶唑酮和 2-苯并恶唑啉酮杂环激活的硫代磷化合物。”

Tadao Ishizuka: "Chiral Synthesis for 2-Amino Alcohols.Facile Preparation of Optically Active Amino Hydroxy Acids of Biological Interest." Tetrahedron. (1993)

Tadao Ishizuka：“2-氨基醇的手性合成。具有生物意义的光学活性氨基羟基酸的轻松制备。”