兰州大学机构库 >生命科学学院
高效地非对映选择性合成1,3-双取代四氢吡喃并[3,4-b]吲哚
Alternative TitleAcid-Catalyzed Highly Diastereoselective and Effective Synthesis of 1,3-Disubstituted Tetrahydropyrano[3,4-b]indoles
赵嘉祯
Thesis Advisor达朝山
2017-05-20
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword不对称合成 非对映选择性 酸催化 oxa-Pictet-Spengler反应 四氢吡喃[3,4-b]吲哚
Abstract

异色满类化合物在药物化学上具有非常广泛的应用,尤其是含有四氢吡喃并[3,4-b]吲哚骨架(THPIs)的化合物,制备这类化合物和相关含氧杂环的重要途径oxa-Pictet-Spengler反应(OPS反应)也因此一直是研究热点。但是,在近30年关于OPS反应的研究中,却很少看到关于1,3-二取代THPIs的详细研究。同时,使用仲色醇作为原料直接合成1,3-二取代的THPIs的报道同样非常少见。

我们课题组通过研究,首次发现三氟乙酸(TFA)可以有效地催化仲色醇与缩醛发生分子间OPS反应,同时高产率(高达>99%)高非对映选择性(>20:1)地合成1,3-二取代的THPIs。此外,我们通过廉价易得的吲哚-3-乙酸合成反应所需的底物仲色醇,并成功地开发出“一锅化”的方法,使醛与原甲酸三甲酯在三氟乙酸的催化下,原位制备得到缩醛,而后直接参与OPS反应,与底物仲色醇反应得到对应的THPIs产物。这种“一锅化”的方法在提高反应效率的同时大大降低了成本,增加了该项工作的实用价值。最后,我们还成功地通过不对称催化得到1,3-二取代的THPIs,并且在该不对称催化中,无论是合成的底物仲色醇,还是最终得到的1,3-二取代的THPIs都被证实具有高度的对映选择性。

Other Abstract

Isochromans are of considerable importance in medicinal chemistry, especially 1,3,4,9-tetrahydropyrano[3,4-b]indole scaffold. The general procedure to prepare THPIs is the time-honored oxa-Pictet-Spengler reaction. However, in previous studies, 1,3-disubstituted tetrahydropyrano[3,4-b]indoles hardly seen to date. Similarly, secondary tryptophols, the straightforward starting materials of 1,3-disubstituted tetrahydropyrano[3,4-b]indoles using in the oxa-Pictet-Spengler reaction, and their synthesis have rarely been reported, either.

We successfully explored for the first time that trifluoroacetic acid (TFA) can effectively catalyze the oxa-Pictet-Spengler reaction of secondary tryptophols and acetals to synthesize 1,3-disubstituted 1,3,4,9-tetrahydropyrano[3,4-b]indoles in high yield (up to >99%) and diastereoselectivity (>20:1). The secondary tryptophols were synthesized from indole-3-acetic acid. The one-pot synthesis of tetrahydropyrano[3,4-b]indoles was successfully developed from secondary tryptophols and in situ prepared acetals from aldehydes and trimethylorthoformate and thus the cost-efficiency of the protocol was effectively enhanced. Finally, the catalytic asymmetric synthesis of the 1,3-disubstituted tetrahydropyrano[3,4-b]indole was also demonstrated after enantioselective achievement of highly enantiopure secondary tryptophols.

URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/221350
Collection生命科学学院
Recommended Citation
GB/T 7714
赵嘉祯. 高效地非对映选择性合成1,3-双取代四氢吡喃并[3,4-b]吲哚[D]. 兰州. 兰州大学,2017.
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