公开(公告)号：US5047528A

公开(公告)日：1991-09-10

申请号：US228821

申请日：1988-08-02

申请人： James P. Kutney ,  Lewis S. L. Choi ,  Jun Nakano ,  Hiroki Tsukamoto ,  Camille A. Boulet ,  Michael McHugh

发明人： James P. Kutney ,  Lewis S. L. Choi ,  Jun Nakano ,  Hiroki Tsukamoto ,  Camille A. Boulet ,  Michael McHugh

IPC分类号： C07D519/04

CPC分类号： C07D519/04

摘要： The present invention relates to the synthesis of dimer alkaloid compounds, particularly those of the Catharantus (Vinca) family, from an indole unit, such as cantharanthine, and a dihydroindole unit, such as vindoline. A multi-step process is disclosed including the steps of (1) of 1,4-reduction of a first dimeric iminium intermediate to an enamine compound by reaction with a 1,4-dihydropyridine compound; (2) oxidative transformation of the resulting enamine to a second iminium intermediate under controlled aeration; (3) reduction of the second iminium intermediate to form the target dimer alkaloid compounds. The entire process can be conducted in a one-pot operation to obtain the target compounds without isolation of the intermediates.

摘要翻译： 本发明涉及二烯生物碱化合物，特别是Catharantus（长春花）家族的二聚生物碱化合物，其可以是吲哚单元，例如cantharanthine，以及二氢吲哚单元，例如乙二氢吲哚。 公开了一种多步骤方法，其包括以下步骤：（1）通过与1,4-二氢吡啶化合物反应1,4-还原第一二聚亚胺中间体至烯胺化合物; （2）在受控通气下将所得烯胺氧化转化为第二亚胺中间体; （3）还原第二亚胺中间体以形成目标二聚体生物碱化合物。 整个过程可以在一锅操作中进行，以获得目标化合物而不分离中间体。

公开(公告)号：USRE37449E1

公开(公告)日：2001-11-13

申请号：US09437626

申请日：1999-11-10

申请人： James P. Kutney ,  Lewis S. L. Choi ,  Jun Nakano ,  Hiroki Tsukamoto ,  Camille A. Boulet ,  Michael McHugh

发明人： James P. Kutney ,  Lewis S. L. Choi ,  Jun Nakano ,  Hiroki Tsukamoto ,  Camille A. Boulet ,  Michael McHugh

IPC分类号： C07D51904

CPC分类号： C07D519/04

摘要： The present invention relates to the synthesis of dimer alkaloid compounds, particularly those of the Catharantus (Vinca) family, from an indole unit, such as cantharanthine, and a dihydroindole unit, such as vindoline. A multi-step process is disclosed including the steps of (1) of 1,4-reduction of a first dimeric iminium intermediate to an enamine compound by reaction with a 1,4-dihydropyridine compound; (2) oxidative transformation of the resulting enamine to a second iminium intermediate under controlled aeration; (3) reduction of the second iminium intermediate to form the target dimer alkaloid compounds. The entire process can be conducted in a one-pot operation to obtain the target compounds without isolation of the intermediates.

摘要翻译： 本发明涉及二烯生物碱化合物，特别是Catharantus（长春花）家族的二聚生物碱化合物，其可以是吲哚单元，例如cantharanthine，以及二氢吲哚单元，例如乙二氢吲哚。 公开了一种多步骤方法，其包括以下步骤：（1）通过与1,4-二氢吡啶化合物反应1,4-还原第一二聚亚胺中间体至烯胺化合物; （2）在受控通气下将所得烯胺氧化转化为第二亚胺中间体; （3）还原第二亚胺中间体以形成目标二聚体生物碱化合物。 整个过程可以在一锅操作中进行，以获得目标化合物而不分离中间体。