A REINVESTIGATION OF MIXED CARBONIC ANHYDRIDE METHOD OF PEPTIDE SYNTHESIS
A REINVESTIGATION OF MIXED CARBONIC ANHYDRIDE METHOD OF PEPTIDE SYNTHESIS
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DOI：
10.1021/ja00995a032
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发表时间：
1967-01-01
影响因子：
15
通讯作者：
CALLAHAN, FM
中科院分区：
文献类型：
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作者：
ANDERSON, GW;ZIMMERMAN, JE;CALLAHAN, FM
研究了混合碳酸氢化法合成多肽过程中影响产率和外消旋的因素。在测试案例中，当形成混合酸酐所需的叔胺至少含有一个N-甲基，并且没有过量使用时，获得了良好的结果，这表明了空间因素的重要性。在乙酸乙酯或四氢呋喃中合成Z-Gly-Phe-Gly-OET时，以过量的三甲胺为三级碱，没有过量的N-甲基吗啉，没有发现完全的环化反应。较灵敏的BZ-Leu-Gly-OET合成方法没有生成1当量N-甲基吗啉的外消旋体，但有2当量的外消旋体生成。本文报道了改变溶剂、温度、混合酸酐形成时间和几种阴离子对消旋反应的影响。给出了恶唑酮消旋的证据。以氯甲酸异丁酯为试剂，产率最高。这里揭示的原理应该对改进其他酰化反应有用。
The factors which affect yield and racemization in peptidesynthesis by the mixed carbonicanhydride method have been investigated. Good results in test cases were obtained when the tertiary amine necessary for formation of the mixed anhydride contained at least one N-methyl group, and it was not used in excess, indicating the importance of steric factors. Reduction of “basicity” of the amine was found to be favorable; complete race-mization was found with an excess of trimethylamine as the tertiary base, and none with an excess of N-methylmorpholine in thetest Z-Gly-Phe-Gly-OEt synthesis in ethyl acetate or tetrahydrofuran. The more sensitive Bz-Leu-Gly-OEt synthesis gave no racemate with 1 equiv of N-methylmorpholine but some racemate with 2 equiv. The effects on racemization of change of solvent, temperature, time allowed for mixed anhydride formation, and several anions are reported. Evidence for racemization via oxazolones is given. Best yields were obtained with isobutyl chloroformate as the reagent. The principles disclosed here should be useful inimproving other acylations.