Viveki Amol B, Mansfield Timothy M, Tran Kevin A, Lenkeit Evan, MacKenzie Kevin R, Young Damian W, Chamakuri Srinivas
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA.
Chemistry. 2023 Oct 2;29(55):e202301888. doi: 10.1002/chem.202301888. Epub 2023 Aug 29.
We report a heterocyclic merging approach to construct novel indazolo-piperazines and indazolo-morpholines. Starting from chiral diamines and amino alcohols, novel regiochemically (1,3 and 1,4) and stereochemically diverse (relative and absolute) cohorts of indazolo-piperazines and indazolo-morpholines were obtained within six or seven steps. The key transformations involved are a Smiles rearrangement to generate the indazole core structure and a late-stage Michael addition to build the piperazine and morpholine heterocycles. We further explored additional vector diversity by incorporating substitutions on the indazole aromatic ring, generating a total of 20 unique, enantiomerically pure heterocyclic scaffolds.
我们报道了一种构建新型吲唑并哌嗪和吲唑并吗啉的杂环合并方法。从手性二胺和氨基醇出发，通过六步或七步反应得到了具有新颖区域化学（1,3和1,4）和立体化学多样性（相对和绝对）的吲唑并哌嗪和吲唑并吗啉系列化合物。所涉及的关键转化包括通过斯迈尔斯重排生成吲唑核心结构以及通过后期迈克尔加成构建哌嗪和吗啉杂环。我们进一步通过在吲唑芳环上引入取代基来探索额外的载体多样性，总共生成了20种独特的对映体纯杂环骨架。
