Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/16502
標題: alpha-胺基酸不對稱合成-由alpha-甲基-反式-肉桂醛製備單環亞胺基內酯及其烷化反應
Asymmetric Synthesis of alpha-Amino Acids-Preparation and Alkylation of Monocyclic Iminolactones Derived From alpha-Methyl-trans-Cinnamaldehyde
作者: 林正坤
Lin, Cheng-Kun
關鍵字: amino acid;胺基酸;asymmetric synthesis;不對稱合成
出版社: 化學系所
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摘要: 
本論文報導三種不同的單環亞胺基內酯的製備暨其在合成alpha-胺基酸上的應用。掌性輔助基 ― alpha-羥基酮74是由alpha-甲基-反式-肉桂醛經由醛基還原、羥基甲基化、雙鍵的Sharpless不對稱雙醇化及後續的IBX氧化二級醇等反應來合成,總產率89%。alpha-羥基酮74分別與Boc-甘胺酸、Boc-丙胺酸、Boc-苯丙胺酸進行酯化反應,接著去保護及合環反應可以得到所需要的掌性楔模 ― 甘胺酸對等物76、丙胺酸對等物92a/93a、苯丙胺酸對等物92c/93c。亞胺基內酯76進行烷化反應僅得到少量的alpha-單取代產物92c/93c,但大部份則為alpha,alpha-雙取代產物94b和94c。亞胺基內酯92a/93a進行烷化反應得到令人滿意的產率 (78-99%) 及高非鏡像超越值 (d.e. >98%;但化合物96d/97d之d.e.為69%) 之alpha-甲基-alpha,alpha-雙取代產物96和97。將亞胺基內酯92c/93c烷化後得到不錯產率 (51-86%) 及尚可的非鏡像超越值 (43-56%) 之alpha-苄基-alpha,alpha-雙取代產物97a/96a、99和100。當使用HMPA或DMPU作為共溶劑時,可加速亞胺基內酯92c/93c的烷化速度,同時可改善烷化產率 (56-99%) 及提升非鏡像超越值 (50-83%)。將雙取代亞胺基內酯水解可得到高產率 (80-98%) 與高鏡像超越值 (98-99%) 的非蛋白質alpha,alpha-雙取代胺基酸及不錯回收產率 (85-92%) 的掌性輔助基74。

This thesis describes the synthesis and their synthetic applications of three kinds of chiral monocyclic iminolactones. The chiral auxiliary ― alpha-hydroxyketone 74 was synthesized from alpha-methyl-trans-cinnamaldehyde through reduction of the aldehyde, methylation of the primary alcohol, Sharpless asymmetric dihydroxylation of the double bond, and oxidation of the secondary alcohol with IBX in an overall 89% yield. Esterification of alpha-hydroxyketone 74 with Boc-glycine, Boc-alanine, and Boc-phenylalanine respectively, followed by deprotection of the Boc group, and cyclization gave the required chiral templates ― glycine equivalent 76, alanine equivalent 92a/93a, and phenylalanine equivalent 92c/93c. Alkylation of iminolactone 76 only generated small amounts of the alpha-monosubstituted products 92c/93c but mostly the undesired alpha,alpha-disubstituted products 94b and 94c. Alkylation of iminolactones 92a/93a afforded the alpha-methyl alpha,alpha-disubstituted products 96 and 97 in good yields (78-99%) and excellent diastereoselectivities (d.e. >98%; except compound 96d/97d with 69% d.e.). Alkylation of iminolactones 92c/93c furnished the alpha-benzyl alpha,alpha-disubstituted products 97a/96a, 99, and 100 in good yields (51-86%) and moderate diastereoselectivities (43-56%). When HMPA or DMPU was used as the cosolvent, the rate of alkylation of iminolactone 92c/93c could be accelerated, the yields were improved (56-99%), and the diastereoselectivities were raised (50-83%). Hydrolysis of the dialkylated iminolactones yielded the nonproteinogenic alpha,alpha-disubstituted alpha-amino acids in good yields (80-98%) and high enantiomeric excesses (98-99%) with good recovery yields (85-92%) of the chiral auxiliary 74.
URI: http://hdl.handle.net/11455/16502
其他識別: U0005-2208200615444400
Appears in Collections:化學系所

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