The uronium/guanidinium Peptide coupling reagents: finally the true uronium salts.
The uronium/guanidinium Peptide coupling reagents: finally the true uronium salts.
复制标题
脲/胍肽偶联试剂：最终是真正的脲盐。
DOI：
10.1002/1521-3773(20020201)41:3
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Bienert,Michael
中科院分区：
文献类型：
--
作者：
Carpino,LouisA;Imazumi,Hideko;El-Faham,Ayman;Ferrer,FernandoJ;Zhang,Chongwu;Lee,Yunsub;Foxman,BruceM;Henklein,Peter;Hanay,Christiane;Mügge,Clemens;Wenschuh,Holger;Klose,Jana;Beyermann,Michael;Bienert,Michael
目前最流行的多肽偶联试剂有膦[1，2](BOP、PyBOP等)。和胍[3](HBTU、HATU等)盐。当1978年首次描述时，HBTU被指定为铀盐1a的结构，大概是通过与前面描述的膦盐的类比来确定的。1993年，我们用同样的方法合成了HATU，[4]，并指定了类似的结构1b，尽管根据目前的知识，两篇论文中引用的1HNMR光谱数据可能会提出不同的建议。一年后，X射线晶体分析、溶液和固体核磁共振光谱表明，在晶态和溶液中[6]和[7，8]的真实结构都是鸟粪异构体2，而不是铀异构体1。这些结果与预期的热力学稳定性是一致的。[9]通过用KOBt[10]和KOAT[13]取代HOBt和Hoat，并快速配制反应混合物，我们现在成功地制备了这两种化合物的原始铀形式。考虑到新的铀盐是比相应的胍异构体更有效的偶联剂，这些结果是特别有趣的。虽然首先在从4-Me-Hoat获得的甲基取代的Hatu衍生物[8]的情况下进行了研究，其中甲基干扰了N-形式的稳定性，但如果注意到O-到N-形式容易被诸如三乙胺的有机碱异构化，则该结构元件不是必需的。在红外光谱中很容易遵循这一过程(见下文)。这种反向重排从未被观察到。用X射线结晶学[14]证实了从钾盐中得到的HBTU和HATU都是O型的(图1)。
Among the currently most popular peptide coupling reagents are the phosphonium [1, 2](BOP, PyBOP, etc.) and guanidinium [3](HBTU, HATU, etc.) salts. When first described in 1978, HBTU was assigned the structure of uronium salt 1a, presumably by analogy with the previously described phosphonium salts. In 1993, we synthesized HATU by using the same method,[4] and the analogous structure 1b was assigned, in spite of the fact that 1H NMR spectroscopic data cited in both papers, viewed in the light of current knowledge,[5] might have suggested otherwise. A year later, X-ray crystallographic analysis and solution and solid-state NMR spectroscopy showed that the true structures in both the crystalline state [6] and in solution [7, 8] were the guanidinium isomers 2 and not the uronium isomers 1. These results are in agreement with expected thermodynamic stabilities.[9] By substituting KOBt [10] and KOAt [13] for HOBt and HOAt, and working up the reaction mixture quickly, we have now succeeded in preparing both these compounds in the originally postulated uronium form. These results are of special interest in view of the fact that the new uronium salts are more efficient coupling reagents than the corresponding guanidinium isomers. Although first examined in the case of a methyl-substituted HATU derivative [8] obtained from 4-Me-HOAt in which the methyl group interferes with the stability of the N-form, this structural element is not essential if attention is paid to the ease of isomerization of the O-to N-form by organic bases such as triethylamine. This process was easily followed in the IR spectrum (see below). The reverse rearrangement has never been observed. X-ray crystallography [14] was used to confirm that both HBTU and HATU obtained from the potassium salts are in the O-form (Figure 1).
登录
查看更多内容
影响因子：
4.9
作者：
Klose, J;Bienert, M;Henklein, P
通讯作者：
Henklein, P
DOI：
10.1002/cber.19791120411
发表时间：
1979
期刊：
Chemische Berichte
影响因子：
--
作者：
H. Kalinowski;H. Kessler
通讯作者：
H. Kessler
DOI：
--
发表时间：
1974
期刊：
影响因子：
--
作者：
P. Dechristopher;J. Adamek;G. D. Lyon;S. A. Klein;R. Baumgarten
通讯作者：
R. Baumgarten
DOI：
--
发表时间：
1977
期刊：
影响因子：
--
作者：
B. Castro;J. Dormoy;B. Dourtoglou;G. Evin;C. Selve;J. Ziegler
通讯作者：
J. Ziegler
1-羟基-7-氮杂苯并三唑钾盐介导的肽的合成。
DOI：
10.1002/chin.199836247
发表时间：
1998
期刊：
ChemInform
影响因子：
--
作者：
H. Gopi;V. V. Babu
通讯作者：
V. V. Babu