Facile Synthesis of Bioactive Amino Alcohols Utilizing 2-Oxazolone Heterocycle

利用 2-恶唑酮杂环轻松合成生物活性氨基醇

• 批准号: 60470150
• 负责人: KUNIEDA Takehisa
• 金额: $ 3.71万
• 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: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60470150/
• 关键词: 2-Oxazolone; Chiral synthon; Amino alcohol; Statine; Hydroxy-glutamic acid; Beta-Latam; Mixed phosphotriester; 合成試薬; 生理活性アミノアルコール; テロメリ化反応; リン酸化試薬

Much synthetic potential of 4,5-unsubstituted 2-oxazolone heterocycle has been explored as a versatile builbing block for vic-amino alcohol structures found in a number of biosctive compounds as well as promising leaving moiety if carboxyl and phosphoryl activation processes.1. Chiral Synthons for 1,2-Amino Alcohols : Good verrsatile strategy from such a simple heterocycle to a wide variety of 1,2-amino alcohols has been developed by highyl regio and stereoselective preparation of chiral synthons, 4-methoxy-5-bromo-2-oxazolidinones, followed by stereospecific and stepwise substitution reactions. This methodology is shown highly promising for the efficient preparation of biologically significant hydroxy smino scids such as 4-amino-3-hydroxy-6-methylheptanoic acid (statine), 3-hydroxy-glutamic acid and 4-amino-3- hydroxylutyric acid (GABOB).2. New Synthetic Reagents : The oxazolone-based compounds, aryl bis(2-oxo-3-oxazolinyl) phosphinate and tris(2-oxo-3-oxazolinyl)phosphine oxide, have been newly introduced as excellent reagents for phosphorylation mild enough to benefit fields ranging from phospholipids to polynucleotides and for <bata>-lactam formation from <bata>-amino acids including a facile preparation of the penam, a basic skeleton of penicillins.

4,5-未取代的2-恶唑酮杂环的合成潜力很大，它可以作为多种生物活性化合物中发现的副氨基醇结构的多用途构建块，并有望在羧基和磷基活化过程中留下大部分。1,2-氨基醇的手性合成：通过高基区和立体选择性制备手性合成物4-甲氧基-5-溴-2-恶唑烷酮，然后进行立体特异性和逐步取代反应，开发了从这种简单的杂环到多种1,2-氨基醇的良好通用策略。该方法在高效制备4-氨基-3-羟基-6-甲基庚酸（他汀）、3-羟基谷氨酸和4-氨基-3-羟基丁酸（GABOB）等具有重要生物学意义的羟基氨基酸方面具有很高的前景。新的合成试剂：以恶唑酮为基础的化合物，芳基二（2-氧-3-恶唑啉基）膦酸酯和三（2-氧-3-恶唑啉基）膦氧化物，已被新引入作为极好的试剂进行温和的磷酸化，从磷脂到多核苷酸，以及从<bata>-氨基酸形成<bata>-内酰胺，包括苯胺的简单制备，青霉素的基本骨架。

项目成果

TOMAHISA NAGAMATSU: TETRAHEDRON LETTERS. 28. (1987)

TOMAHISA NAGAMATSU：四面体字母。

国枝武久: 薬学雑誌. 108. (1988)

Takehisa Kunieda：制药杂志 108。（1988）

Takehisa,Kunieda: "3-Acyl-2-oxazolone/Zirconium Complexes as Exxellent Reagents for Highyl Regioselective Acylation of Polyalcohols." Tetrahedron Letters. 26. 1977-1980 (1985)

Takehisa,Kunieda：“3-酰基-2-恶唑酮/锆配合物作为多元醇高基区域选择性酰化的优秀试剂。”

Tomohisa Nagamatsu: Tetrahedron Letters. 28. 2375-2378 (1987)

长松智久：四面体字母。

Tadao,Ishizuka: "Mild and Selective Ring-cleavage of Cyclic Carbamtes to Amino Alcohols." Tetrahedron Letters. 28. 4185-4188 (1987)

Tadao，Ishizuka：“环状氨基甲酸酯温和选择性环裂解为氨基醇。”