Département de Chimie, Université de Montréal, C.P.6128. Succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7.
J Org Chem. 2012 Aug 3;77(15):6414-22. doi: 10.1021/jo3005809. Epub 2012 Jul 24.
Protected enantiopure 2-pyrrolylalanine was synthesized for application in peptide science as an electron-rich arylalanine (histidine) analog with π-donor capability. (2S)-N-(Boc)-N'-(Phenylsulfonyl)-, (2S)-N,N'-bis-(phenylsulfonyl)-, and (2S)-N,N'-bis-(Boc)-3-(2-pyrrolyl)alanines (10, 3, and 14, respectively) were made in 13-17% overall yields and six to seven steps from oxazolidine β-methyl ester 4. Homoallylic ketone 5 was prepared by a copper-catalyzed cascade addition of vinylmagnesium bromide to ester 4 and converted to pyrrolyl amino alcohol 7 by olefin oxidation and Paal-Knorr condensation. Protecting group shuffle and oxidation of the primary alcohol enabled the synthesis of pyrrolylalanines. The bis-Boc analog 14 proved useful in peptide chemistry and was employed to make N-acetyl-pyrrolylalaninyl-proline N''-methylamide 25. A study of the influence of the pyrrole moiety on the prolyl amide isomer equilibrium of 25 using (1)H NMR spectroscopy in chloroform, DMSO, and water demonstrated that the pyrrolylalanine peptide exhibited behavior and conformations different from those of other arylalanine analogs.
保护手性纯 2-吡咯基丙氨酸被合成用于肽科学，作为具有π-供体能力的富电子芳基丙氨酸（组氨酸）类似物。（2S）-N-（Boc）-N' -（苯磺酰基）-，（2S）-N，N'-双-（苯磺酰基）-和（2S）-N，N'-双-（Boc）-3-（2-吡咯基）丙氨酸（10、3 和 14，分别）以 13-17%的总收率和六到七个步骤从恶唑烷 β-甲酯 4 制得。偕丙位烯酮 5 通过铜催化的乙烯基溴化镁对酯 4 的级联加成制备，并通过烯烃氧化和 Paal-Knorr 缩合转化为吡咯基氨基醇 7。保护基的交换和伯醇的氧化使吡咯丙氨酸的合成成为可能。双 Boc 类似物 14 在肽化学中非常有用，并被用于合成 N-乙酰-吡咯丙氨酸-脯氨酸 N''-甲基酰胺 25。使用（1）H NMR 光谱在氯仿、DMSO 和水中研究吡咯部分对 25 的脯氨酰酰胺异构体平衡的影响表明，吡咯丙氨酸肽表现出与其他芳基丙氨酸类似物不同的行为和构象。
