化学
立体选择性
区域选择性
儿茶酚
立体化学
氧化剂
组合化学
有机化学
催化作用
作者
Rebecca Roddan,Fabiana Subrizi,Joseph Broomfield,John M. Ward,Nicholas H. Keep,Helen C. Hailes
出处
期刊:Organic Letters
[American Chemical Society]
日期:2021-08-06
卷期号:23 (16): 6342-6347
被引量:14
标识
DOI:10.1021/acs.orglett.1c02110
摘要
Tetrahydroprotoberberine and protoberberine alkaloids are a group of biologically active natural products with complex molecular scaffolds. Isolation from plants is challenging and stereoselective synthetic routes, particularly of methylated compounds are limited, reducing the potential use of these compounds. In this work, we describe chemoenzymatic cascades toward various 13-methyl-tetrahydroprotoberberbine scaffolds using a stereoselective Pictet-Spenglerase, regioselective catechol O-methyltransferases and selective chemical Pictet-Spengler reactions. All reactions could be performed sequentially, without the workup or purification of any synthetic intermediates. Moreover, the naturally occurring alkaloids have the (+)-configuration and importantly here, a strategy to the (−)-isomers was developed. A methyl group at C-8 was also introduced with some stereocontrol, influenced by the stereochemistry at C-13. Furthermore, a single step reaction was found to convert tetrahydroprotoberberine alkaloids into the analogous protoberberine scaffold, avoiding the use of harsh oxidizing conditions or a selective oxidase. This work provides facile, selective routes toward novel analogues of bioactive alkaloids.
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