手性、非外消旋 1,2,4-三取代 1,4-二氮杂环丁烷的固相有机合成，具有高 σ 受体亲和力。
Solid-phase organic synthesis of chiral, non-racemic 1,2,4-trisubstituted 1,4-diazepanes with high σ receptor affinity.
机构信息
Institut für Pharmazeutische und Medizinische Chemie, Universität Münster, Münster, Germany.
Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms-Universität Münster, Münster, Germany.
出版信息
Arch Pharm (Weinheim). 2018 Jan;351(1). doi: 10.1002/ardp.201700334. Epub 2017 Dec 11.
The aim of this work was to transfer the established chiral-pool synthesis of 1,2,4-trisubstituted 1,4-diazepanes in solution on the solid phase. For this purpose, (S)-configured amino acids, (S)-alanine, and (S)-leucine, with a small methyl and a larger isobutyl moiety were attached to the solid support 9 by reductive amination. After five reaction steps on the solid support, the 1,4-diazepanes (S)-19a,b were cleaved off and reductively alkylated to afford the 1,2,4-trisubstituted 1,4-diazepanes (S)-20a and (S)-21b, respectively. Both compounds show high σ affinity and selectivity over the σ subtype.
这项工作的目的是将已建立的手性池合成 1,2,4-三取代的 1,4-二氮杂环己烷从溶液转移到固相上。为此，（S）构型的氨基酸（S）-丙氨酸和（S）-亮氨酸，带有一个小甲基和一个更大的异丁基部分，通过还原胺化反应连接到固体载体 9 上。在固体载体上进行了五个反应步骤后，1,4-二氮杂环己烷（S）-19a,b 被裂解下来，并进行还原烷基化，分别得到 1,2,4-三取代的 1,4-二氮杂环己烷（S）-20a 和（S）-21b。这两种化合物对 σ 亚型具有高的 σ 亲和力和选择性。
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