Instituto de Productos Naturales y Agrobiología del CSIC, Avda. Astrofísico Fco. Sánchez, 3, 38206 La Laguna, Tenerife, Spain.
BIOSIGMA, Antonio Domínguez Alfonso 16, 38003 Santa Cruz de Tenerife, Tenerife, Spain.
J Org Chem. 2021 Feb 5;86(3):2796-2809. doi: 10.1021/acs.joc.0c02751. Epub 2021 Jan 12.
Readily available, low-cost 4-hydroxy-l-proline (Hyp) is introduced as a "doubly customizable" unit for the generation of libraries of structurally diverse compounds. Hyp can be cleaved at two points, followed by the introduction of new functionalities. In the first cycle, the removal and replacement of the carboxylic group are carried out, followed (second cycle) by the scission of the 4,5-position and manipulation of the resulting chains. In this way, three new chains are generated and can be transformed independently to afford a diversity of products with tailored substituents, such as β-amino aldehydes, diamines, β-amino acid derivatives, including N-alkylated ones, or modified peptides. Many of these products are high-profit compounds but, in spite of their commercial value, are still scarce. Moreover, the process takes place with stereochemical control, and either pure or isomers can be obtained with small variations of the synthetic route.
易于获得、低成本的 4-羟基-L-脯氨酸（Hyp）被引入作为生成结构多样的化合物库的“双重可定制”单元。Hyp 可以在两个点断裂，然后引入新的官能团。在第一个循环中，去除和替换羧酸基团，然后（第二个循环）断裂 4,5-位并操纵所得链。通过这种方式，生成了三个新链，可以独立转化，得到具有定制取代基的各种产物，例如β-氨基醛、二胺、β-氨基酸衍生物，包括 N-烷基化产物或修饰肽。其中许多产品都是高利润化合物，但尽管它们具有商业价值，仍然稀缺。此外，该过程具有立体化学控制，并且可以通过合成路线的微小变化获得纯或异构体。
