Enantioselective Total Synthesis of (+)-Lysergic Acid, (+)-Lysergol, and (+)-Isolysergol by Palladium-Catalyzed Domino Cyclization of Allenes Bearing Amino and Bromoindolyl Groups
Enantioselective Total Synthesis of (+)-Lysergic Acid, (+)-Lysergol, and (+)-Isolysergol by Palladium-Catalyzed Domino Cyclization of Allenes Bearing Amino and Bromoindolyl Groups
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DOI：
10.1021/jo102388e
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发表时间：
2011-04-01
影响因子：
3.6
通讯作者：
Ohno, Hiroaki
中科院分区：
文献类型：
--
作者：
Inuki, Shinsuke;Iwata, Akira;Ohno, Hiroaki
描述了生物学上重要的吲哚生物碱 (+)-麦角醇、(+)-异麦角醇和 (+)-麦角酸的对映选择性全合成。这些全合成的关键特征包括（1）通过L-丝氨酸衍生的2-乙炔基氮丙啶和甲醛之间的Pd（0）和In（I）介导的还原偶联反应轻松合成手性1,3-氨基醇； (2) Cr(II)/Ni(0)介导的吲哚-3-乙醛与碘炔的Nozaki-Hiyama-Kishi (NHK)反应； (3) Pd(0) 催化的带有氨基和溴吲哚基的丙二烯的多米诺环化。这种多米诺环化使得能够直接构建麦角生物碱骨架的C/D环系统，以及通过将联烯轴向手性转移到中心手性来创建C5立体中心。
Enantioselective total synthesis of the biologically important indole alkaloids (+)-lysergol, (+)-isolysergol, and (+)-lysergic acid is described. Key features of these total synthesis include (1) a facile synthesis of a chiral 1,3-amino alcohol via the Pd(0)- and In(I)-mediated reductive coupling reaction between L-serine-derived 2-ethynylaziridine and formaldehyde; (2) the Cr(II)/Ni(0)-mediated Nozaki-Hiyama-Kishi (NHK) reaction of an indole-3-acetaldehyde with iodoalkyne; and (3) Pd(0)-catalyzed domino cyclization of an allene bearing amino and bromoindolyl groups. This domino cyclization enabled direct construction of the C/D ring system of the ergot alkaloids skeleton, as well as the creation of the C5 stereogenic center with transfer of the allenic axial chirality to the central chirality.