Enzymatic Synthesis of C-Terminal Arylamides of Amino Acids and Peptides
Enzymatic Synthesis of C-Terminal Arylamides of Amino Acids and Peptides
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DOI：
10.1021/jo900634g
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发表时间：
2009-08-07
影响因子：
3.6
通讯作者：
Quaedflieg, Peter J. L. M.
中科院分区：
文献类型：
--
作者：
Nuijens, Timo;Cusan, Claudia;Quaedflieg, Peter J. L. M.
本文介绍了一种温和、经济的化学-酶法合成氨基酸和肽的C-端芳酰胺的方法。使用工业丝氨酸蛋白酶Alcalase在接近无水的条件下，N-Cbz保护的氨基酸和肽的C-末端芳基酰胺可以从相应的C-末端羧酸，甲基（Me）或苄基（Bn）酯以高化学纯度和对映异构体和非对映异构体纯度获得。产率范围在50%和95%之间，这取决于芳基取代基的大小和吸电子取代基的存在。甚至在存在各种未保护的侧链官能团如β/γ-羧基、羟基和胍基的情况下，也可以获得完全的α-C-末端选择性。此外，使用半胱氨酸蛋白酶木瓜蛋白酶和脂肪酶Cal-B以高产率得到酰苯胺。与最先进的化学方法相比，化学-酶法合成芳基酰胺被证明是完全无外消旋的。
A mild and cost-efficient chemo-enzymatic method for the synthesis of C-terminal arylamides of amino acid and peptides is described. Using the industrial serine protease Alcalase under near-anhydrous conditions, C-terminal arylamides of N-Cbz-protected amino acids and peptides could be obtained from the corresponding C-terminal carboxylic acids, methyl (Me) or benzyl (Bn) esters, in hi-h chemical and enantio- and diastereomeric purities. Yields ranged between 50% and 95% depending on the size of the aryl substituents and the presence of electron-withdrawing substituents. Complete (alpha-C-terminal selectivity could be obtained even in the presence of various unprotected side-chain functionalities such as beta/gamma-carboxyl, hydroxyl, and guanidino groups. In addition, the use of the cysteine protease papain and the lipase Cal-B gave anilides in high yields. The chemo-enzymatic synthesis of arylamides proved to be completely free of racemization, in contrast to the state-of-the-art chemical methods.