Autoxidation of a C2-Olefinated Dihydroartemisinic Acid Analogue to Form an Aromatic Ring: Application to Serrulatene Biosynthesis.
Autoxidation of a C2-Olefinated Dihydroartemisinic Acid Analogue to Form an Aromatic Ring: Application to Serrulatene Biosynthesis.
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C2-烯化二氢青蒿酸拮抗剂的自氧化形成芳环：应用于锯齿素生物合成。
DOI：
10.1021/acs.jnatprod.1c01101
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发表时间：
2022-04-22
影响因子：
5.1
通讯作者：
Yoshimoto, Francis K.
中科院分区：
文献类型：
--
作者：
Varela, Kaitlyn;Al Mahmud, Hafij;Arman, Hadi D.;Martinez, Luis R.;Wakeman, Catherine A.;Yoshimoto, Francis K.
双氢青蒿酸（DHAA）是一种植物天然产物，在空气中会发生自发的内过氧化物级联反应生成青蒿素。内过氧化物官能团赋予青蒿素杀死恶性疟原虫（导致疟疾的寄生虫）的生物活性。为了加深对该级联反应机理的理解，合成了一种在C2-位上具有双键的DHAA衍生物2，3-二脱氢二氢青蒿酸（2，3-didehydro-DHAA）。当2，3-二脱氢-DHAA随时间暴露于空气时，该化合物主要经历芳构化，而不是形成内过氧化物。这种烯化DHAA类似物揭示了单烯烃官能团引发内过氧化物形成级联反应以从DHAA产生青蒿素的需要。此外，该芳构化过程被用来说明不同的植物天然产物二氢锯齿烯的自氧化过程，以形成锯齿烯中的芳环。这种自发芳构化过程在其它天然产物如leubethanol和erogorgiaene中也有应用。由于它们与抗菌天然产物在结构上的相似性，本研究中合成的化合物进行了生物活性测试。一组测试化合物对细菌病原体金黄色葡萄球菌和真菌病原体新型隐球菌具有12.5至25 μg/mL的最小抑制浓度（MIC）值。
Dihydroartemisinic acid (DHAA) is a plant natural product that undergoes a spontaneous endoperoxide-forming cascade reaction to yield artemisinin in the presence of air. The endoperoxide functional group gives artemisinin its biological activity that kills Plasmodium falciparum, the parasite that causes malaria. To enhance our understanding of the mechanism of this cascade reaction, 2,3-didehydrodihydroartemisinic acid (2,3-didehydro-DHAA), a DHAA derivative with a double bond at the C2-position, was synthesized. When 2,3-didehydro-DHAA was exposed to air over time, instead of forming an endoperoxide, this compound predominantly underwent aromatization. This olefinated DHAA analogue reveals the requirement of a monoalkene functional group to initiate the endoperoxide-forming cascade reaction to yield artemisinin from DHAA. In addition, this aromatization process was exploited to illustrate the autoxidation process of a different plant natural product, dihydroserrulatene, to form the aromatic ring in serrulatene. This spontaneous aromatization process has applications in other natural products such as leubethanol and erogorgiaene. Due to their similarity in structure to antimicrobial natural products, the synthesized compounds in this study were tested for biological activity. A group of the tested compounds had minimum inhibitory concentration (MIC) values ranging from 12.5 to 25 μg/mL against the bacterial pathogen Staphylococcus aureus and the fungal pathogen Cryptococcus neoformans.
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影响因子：
4.3
作者：
Incerti-Pradillos, Celia A.;Kabeshov, Mikhail A.;Malkov, Andrei V.
通讯作者：
Malkov, Andrei V.
影响因子：
2.1
作者：
Brown, GD;Sy, LK
通讯作者：
Sy, LK
影响因子：
1.8
作者：
Harmata, M;Hong, XC
通讯作者：
Hong, XC
影响因子：
6.4
作者：
Fey PD;Endres JL;Yajjala VK;Widhelm TJ;Boissy RJ;Bose JL;Bayles KW
通讯作者：
Bayles KW
影响因子：
3.9
作者：
JOHNSON, MA;CROTEAU, R
通讯作者：
CROTEAU, R