Study of the Reaction of Unprotected Amino Acids in Aqueous Media and its Application for the Short-Step Synthesis of Ergot Alkaloids

水介质中未保护氨基酸的反应研究及其在麦角生物碱短步合成中的应用

• 批准号: 13672237
• 负责人: YOKOYAMA Yuusaku
• 金额: $ 2.3万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672237/
• 关键词: Bemztrvptophan; Amino acids; Bromination; Racemization; N-Methvlamino acids; Protecting groups; Aqueous media; Tryptophan; ベンズインドール; ビニル化; リゼルギン酸; Heck反応; パラジウム触媒; アリル化

1)Several free amino acids, phrnylglycine, phenylalanine, tryptophan were heated at 100-130℃ under alkaline or acidic condition in water or various polar organic solvents.Although serious racemization and decomposition occurred in polar organic solvents such as DMF, DMSO, or ethylene glycol under alkaline condition (K_2CO_3, KOH, Et_3N), those phenomenon did not occur, or were largely decreased in water or water containing organic solvent under the same alkaline condition.2)Bromination of unprotected phenylalanine with bromoisocyanuric acid sodium salt in strong acidic solution (60% H_2SO_4) gave the mixture of 2-bromo-and 4-bromophenylalanine in 31% and 58% yield, respectively.3)The reaction of benz[e]-, benz[f]-, benz[g] indoles with dl-serine in the presence of Ac_2O in AcOH at 50-60℃ gave the corresponding dl-N-acetylbenztryptophanes in 42-59% yield accompanied with 2,3-di-subusituted derivatives as by-products. Kinetic resolution of the above dl-N-acetylbenztryptophans by Aspergillus acylase gave corresponding optically pure(S)-benztryptophans.

1)在碱性或酸性条件下，在水或各种极性有机溶剂中加热100-130℃，几种游离氨基酸（苯丙氨酸、甘氨酸、色氨酸）在DMF、DMSO或乙二醇等极性有机溶剂中，虽然在碱性条件下会发生严重的外消旋和分解，但在碱性条件下，它们的外消旋和分解反应仍很剧烈（K_2CO_3，KOH，Et_3N），则无上述现象发生，或在相同碱性条件下，在水或含水有机溶剂中，强酸性条件下溴代异氰尿酸钠盐对未保护苯丙氨酸的溴化反应3）苯并[e]-、苯并[f]-、苯并[c]-、苯并[d]-、苯并[e]-、苯并[f]-、苯并[苯并[g]吲哚与dl-丝氨酸在Ac_2O存在下于AcOH中于50-60℃反应生成相应的dl-N-乙酰基苯并[g]吲哚，产率为42-59%，并伴有2，3-二取代衍生物。用曲霉酰化酶动力学拆分上述dl-N-乙酰苯并吡喃，得到相应的光学纯（S）-苯并吡喃。

项目成果

Yuusaku Yokoyama: "N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan Methyl Ester, A Key Intermediate in the Synthesis of Optically Active....."Heterocycles. 55(4). 653-659 (2001)

Yuusaku Yokoyama：“N-Boc-4-溴-N-甲基-1-甲苯磺酰基-D-色氨酸甲酯，光学活性合成中的关键中间体......”杂环。

Hikawa H, Yokoyama Y, Murakami Y: "A Short Synthesis of Optically Active γ,γ-Dimethylallyltryptophan (DMAT)."Synthesis. 214-216 (2000)

Hikawa H、Yokoyama Y、Murakami Y：“光学活性 γ,γ-二甲基烯丙基色氨酸 (DMAT) 的简短合成。”合成 214-216 (2000)。

Yokoyama Y, Tsuruta K, Murakami Y: "A Study for Palladium-Catalyzed Chemoselective Vinylation at C-5 Position of 4-Bromo-1-tosylindoles"Heterocycles. 56. 525-529 (2002)

Yokoyama Y、Tsuruta K、Murakami Y：“4-Bromo-1-tosylindoles C-5 位点钯催化化学选择性乙烯基化的研究”杂环。

Yuusaku Yokoyama: "Does Water Suppress the Racemization and Decomposition of Amino Acids?"J.Chem.Soc.,Perkin Trans.1. 1431-1434 (2001)

Yuusaku Yokoyama：“水会抑制氨基酸的外消旋化和分解吗？”J.Chem.Soc.，Perkin Trans.1。

Yuusaku Yokoyama: "A Study for Palladium-Catalyzed Chemoselective Vinylation at C-3 Position of 4-Bromo-1-Tosylindole."Heterocycles. 56. 525-529 (2002)

Yuusaku Yokoyama：“4-Bromo-1-Tosylindole C-3 位点钯催化化学选择性乙烯基化的研究”。杂环。