Accurate prediction of rate constants of Diels-Alder reactions and application to design of Diels-Alder ligation.
Accurate prediction of rate constants of Diels-Alder reactions and application to design of Diels-Alder ligation.
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Diels-Alder 反应速率常数的准确预测及其在 Diels-Alder 连接设计中的应用。
DOI：
10.1039/c2ob07079k
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发表时间：
2012-04
影响因子：
3.2
通讯作者：
Guo, Qing-Xiang
中科院分区：
文献类型：
--
作者：
Tang, Shi-Ya;Shi, Jing;Guo, Qing-Xiang
Bioorthogonal reactions are useful tools to gain insights into the structure, dynamics, and function of biomolecules in the field of chemical biology. Recently, the Diels-Alder reaction has become a promising and attractive procedure for ligation in bioorthogonal chemistry because of its higher rate and selectivity in water. However, a drawback of the previous Diels-Alder ligation is that the widely used maleimide moiety as a typical Michael acceptor can readily undergo Michael addition with nucleophiles in living systems. Thus, it is important to develop a nucleophile-tolerant Diels-Alder system in order to extend the scope of the application of Diels-Alder ligation. To solve this problem, we found that the theoretical protocol M06-2X/6-31+G(d)//B3LYP/6-31G(d) can accurately predict the activation free energies of Diels-Alder reactions with a precision of 1.4 kcal mol(-1) by benchmarking the calculations against the 72 available experimental data. Subsequently, the electronic effect and ring-strain effect on the Diels-Alder reaction were studied to guide the design of the new dienophiles. The criteria of the design is that the designed Diels-Alder reaction should have a lower barrier than the Michael addition, while at the same time it should show a similar (or even higher) reactivity as compared to the maleimide-involving Diels-Alder ligation. Among the designed dienophiles, three substituted cyclopropenes (i.e. 1,2-bis(trifluoromethyl)-, 1,2-bis(hydroxylmethyl)- and 1,2-bis(hydroxylmethyl)-3-carboxylcyclopropenes) meet our requirements. These substituted cyclopropene analogs could be synthesized and they are thermodynamically stable. As a result, we propose that 1,2-bis(trifluoromethyl)-, 1,2-bis(hydroxylmethyl)- and 1,2-bis(hydroxylmethyl)-3-carboxylcyclopropenes may be potential candidates for efficient and selective Diels-Alder ligation in living systems.
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影响因子：
3.6
作者：
Froese, RDJ;Coxon, JM;Morokuma, K
通讯作者：
Morokuma, K
影响因子：
2.4
作者：
T. Tiefenbrunn;P. Dawson
通讯作者：
T. Tiefenbrunn;P. Dawson
影响因子：
3.2
作者：
P. van Swieten;M. Leeuwenburgh;B. Kessler;H. Overkleeft
通讯作者：
P. van Swieten;M. Leeuwenburgh;B. Kessler;H. Overkleeft
DOI：
10.1021/jp050536c
发表时间：
2005-06
期刊：
The journal of physical chemistry. A
影响因子：
--
作者：
Yan Zhao;D. Truhlar
通讯作者：
Yan Zhao;D. Truhlar
影响因子：
15
作者：
Wang, Q;Chan, TR;Finn, MG
通讯作者：
Finn, MG