通过氧化吲哚烯醇盐的高度立体选择性烷基化高效不对称合成新型胃泌素受体拮抗剂AG-041R。
Efficient asymmetric synthesis of novel gastrin receptor antagonist AG-041R via highly stereoselective alkylation of oxindole enolates.
作者信息
Emura Takashi, Esaki Toru, Tachibana Kazutaka, Shimizu Makoto
机构信息
Chemistry Research Department 1, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
出版信息
J Org Chem. 2006 Oct 27;71(22):8559-64. doi: 10.1021/jo061541v.
An efficient method for asymmetric synthesis of the potent Gastrin/CCK-B receptor antagonist AG-041R was developed. Core oxindole stereochemistry was established by asymmetric alkylation of oxindole enolates with bromoacetic acid esters, using l-menthol as a chiral auxiliary. The key alkylation reaction of the oxindole enolates generated tetrasubstituted chiral intermediates with high diastereoselectivity. The stereoselective alkylation reactions are described in detail.
开发了一种高效的强力胃泌素/胆囊收缩素B受体拮抗剂AG-041R的不对称合成方法。利用L-薄荷醇作为手性助剂，通过吲哚酮烯醇化物与溴乙酸酯的不对称烷基化反应，建立了核心吲哚酮立体化学。吲哚酮烯醇化物的关键烷基化反应以高非对映选择性生成了四取代手性中间体。详细描述了立体选择性烷基化反应。
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