Total syntheses of β-carboline alkaloids, (R)-(_)-pridindolol K1, (R)-(_)-pyridindolol K2, and (R)-(_)-pyridindolol
Total syntheses of β-carboline alkaloids, (R)-(_)-pridindolol K1, (R)-(_)-pyridindolol K2, and (R)-(_)-pyridindolol
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DOI：
10.1021/jo0105585
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发表时间：
2001-12-28
影响因子：
3.6
通讯作者：
Hibino, S
中科院分区：
文献类型：
--
作者：
Kanekiyo, N;Kuwada, T;Hibino, S
本文报道了β-咔啉生物碱（R）-（-）-吡啶二醇（1，5和6）的全合成.所涉及的两个关键步骤是（1）3-烯基吲哚-2-醛肟10的热电环化反应和（2）3-炔基吲哚-2-醛肟11的热环化，以构建β-咔啉N-氧化物8，其在用乙酸酐加热并随后用三氟甲磺酸酐处理后得到三氟甲磺酸酯18。18与乙烯基锡烷进行Stille偶联反应，然后裂解三乙醚，得到1-乙烯基-3-羟甲基-β-咔啉（7a）。7a的随后乙酰化产生乙酸酯7 b，其通过AD-mix-beta进行Sharpless不对称1，2-二羟基化以产生（R）-（-）-吡啶醇K2（6）。6用Ac_2O和可力丁选择性乙酰化生成（R）-（-）-吡啶醇K_1（5）。与此相反，6水解得到（R）-（-）-吡啶二醇（1）。
The total syntheses of beta -carboline alkaloids, (R)-(-)-pyridindolols (1, 5, and 6) are described. The two key steps involved are (1) a thermal electrocyclic reaction of the 3-alkenylindole-2-aldoxime 10 and (2) a thermal cyclization of 3-alkynylindole-2-aldoxime 11 to construct the beta -carboline N-oxides 8, which upon heating with acetic anhydride and sequential treatment with trifluoromethanesulfonic anhydride gave the triflates 18. The Stille coupling reaction of 18 with vinylstannane, followed by cleavage of MOM ether, afforded the 1-ethenyl-3-hydroxymethyl-beta -carboline (7a). Subsequent acetylation of 7a yielded the acetate 7b, which was subjected to the Sharpless asymmetric 1,2-dihydroxylation by AD-mix-beta to produce (R)-(-)-pyridindolol K2 (6). Selective acetylation of 6 was effected by Ac2O and collidine to form (R)-(-)-pyridindolol K1 (5). By contrast, hydrolysis of 6 provided (R)-(-)-pyridindolol (1).