Regioselective Incorporation of Backbone Constraints Compatible with Traditional Solid-Phase Peptide Synthesis
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- 作者：Agustina La Venia ; Barbora Lemrov谩 ; Viktor Krch艌谩k
- 刊名：ACS Combinatorial Science
- 出版年：2013
- 出版时间：January 14, 2013
- 年：2013
- 卷：15
- 期：1
- 页码：59-72
- 全文大小：613K
- 年卷期：v.15,no.1(January 14, 2013)
- ISSN：2156-8944
文摘
A protected aldehyde was attached via a two-carbon spacer to a peptide backbone amide nitrogen during a traditional Merrifield solid-phase synthesis. Acid-mediated unmasking of the aldehyde triggered the regioselective formation of cyclic N-acyliminiums between the aldehyde and the neighboring peptide amide nitrogen. In the absence of an internal nucleophile, the cyclic iminiums formed dihydropyrazinones, a six-membered peptide backbone constraint between two peptide amides. In the presence of an internal nucleophile, tetrahydropyrazinopyrimidinediones or tetrahydroimidazopyrazinediones were formed via tandem N-acyliminium ion cyclization-nucleophilic addition. The outcome of this nucleophilic addition was dependent on the substituent on the nitrogen nucleophile.