Ugi 4-CR/Pictet-Spengler reaction as a short route to tryptophan-derived peptidomimetics
Ugi 4-CR/Pictet-Spengler reaction as a short route to tryptophan-derived peptidomimetics
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DOI：
10.1039/c2ob26301g
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发表时间：
2012-01-01
影响因子：
3.2
通讯作者：
Silvani, Alessandra
中科院分区：
文献类型：
--
作者：
Lesma, Giordano;Cecchi, Roberto;Silvani, Alessandra
本文报道了一种从Ugi 4-CR/Pictet-Spengler反应序列合成1，2，3，4-四氢-β-咔啉（THBC）四环肽模拟物的两步有效路线。适当地，N-保护的2-氨基乙醛第一次被用作Ugi四组分反应中的羰基组分，从而为在相同作用中使用N-保护的α-氨基酸衍生的醛开辟了道路。所获得的支架的潜力与进一步衍生化的可能性与所需的pharmacophoric基团，在两个终端的酸和胺官能团，用于开发构象受限的含葡聚糖的肽配体。广泛的分子建模和H-1 NMR研究突出了这些拟肽化合物之一的稳健的、折叠的、β-转角样构象。
We report here a two step efficient route for the synthesis of 1,2,3,4-tetrahydro-beta-carboline (THBC)-based tetracyclic peptidomimetics from a Ugi 4-CR/Pictet-Spengler reaction sequence. Suitably N-protected 2-aminoacetaldehyde was for the first time applied as the carbonyl component in a Ugi four-component reaction, opening the way to the employment of N-protected alpha-amino acid-derived aldehydes in the same role. The potential of the obtained scaffolds is related to the possibility of further derivatization with the desired pharmacophoric groups, on both the terminal acid and amine functional groups, for the development of conformationally constrained tryptophan-containing peptide ligands. Extensive molecular modeling and H-1 NMR studies highlighted a robust, folded, beta-turn-like conformation for one of these peptidomimetic compounds.