Dipartimento di Scienze Farmaceutiche, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy.
Dipartimento di Chimica e Tecnologie Chimiche (CTC), Via Ponte P. Bucci, Cubo 12D, Università della Calabria, I-87036 Arcavacata di Rende (CS), Italy.
Molecules. 2020 Mar 13;25(6):1313. doi: 10.3390/molecules25061313.
A synthetic strategy for the preparation of two orthogonally protected methyl esters of the non-proteinogenic amino acid 2,3-l-diaminopropanoic acid (l-Dap) was developed. In these structures, the base-labile protecting group 9-fluorenylmethyloxycarbonyl (Fmoc) was paired to the -toluensulfonyl (tosyl, Ts) or acid-labile -butyloxycarbonyl (Boc) moieties. The synthetic approach to protected l-Dap methyl esters uses appropriately masked 2,3-diaminopropanols, which are obtained via reductive amination of an aldehyde prepared from the commercial amino acid -Fmoc---butyl-d-serine, used as the starting material. Reductive amination is carried out with primary amines and sulfonamides, and the process is assisted by the Lewis acid Ti(OPr). The required carboxyl group is installed by oxidizing the alcoholic function of 2,3-diaminopropanols bearing the tosyl or benzyl protecting group on the 3-NH site. The procedure can easily be applied using the crude product obtained after each step, minimizing the need for chromatographic purifications. Chirality of the carbon atom of the starting d-serine template is preserved throughout all synthetic steps.
开发了一种用于制备非蛋白氨基酸 2,3-l-二氨基丙酸（l-Dap）的两种正交保护的甲酯的合成策略。在这些结构中，碱不稳定的保护基团 9-芴甲氧羰基（Fmoc）与 -甲苯磺酰基（tosyl，Ts）或酸不稳定的 -叔丁氧羰基（Boc）部分配对。保护的 l-Dap 甲酯的合成方法使用适当屏蔽的 2,3-二氨基丙醇，这些醇是通过商业氨基酸 -Fmoc---丁基-d-丝氨酸制备的醛的还原胺化获得的，作为起始原料。还原胺化是用伯胺和磺酰胺进行的，路易斯酸 Ti(OPr) 辅助该过程。所需的羧基基团是通过氧化带有 tosyl 或苄基保护基的 3-NH 位上的 2,3-二氨基丙醇的醇官能团来安装的。可以通过使用在每个步骤后获得的粗产物轻松应用该程序，最大程度地减少对色谱纯化的需求。起始 d-丝氨酸模板碳原子的手性在整个合成步骤中都得到保留。
