6040-37-5Relevant articles and documents
Total synthesis of (+)-pleuromutilin
Fazakerley, Neal J.,Helm, Matthew D.,Procter, David J.
, p. 6718 - 6723 (2013)
The first enantiospecific total synthesis of the antibacterial natural product (+)-pleuromutilin has been achieved. The approach includes the synthesis of a non-racemic cyclisation substrate from (+)-trans-dihydrocarvone, a highly selective SmI2-mediated cyclisation cascade, an electron transfer reduction of a hindered ester, and the first efficient conversion of (+)-mutilin to the target. Copyright
Directed C-H Bond Oxidation of (+)-Pleuromutilin
Ma, Xiaoshen,Kucera, Roman,Goethe, Olivia F.,Murphy, Stephen K.,Herzon, Seth B.
, p. 6843 - 6892 (2018)
Antibiotics derived from the diterpene fungal metabolite (+)-pleuromutilin (1) are useful agents for the treatment Gram-positive infections in humans and farm animals. Pleuromutilins elicit slow rates of resistance development and minimal cross-resistance with existing antibiotics. Despite efforts aimed at producing new derivatives by semisynthesis, modification of the tricyclic core is underexplored, in part due to a limited number of functional group handles. Herein, we report methods to selectively functionalize the methyl groups of (+)-pleuromutilin (1) by hydroxyl-directed iridium-catalyzed C-H silylation, followed by Tamao-Fleming oxidation. These reactions provided access to C16, C17, and C18 monooxidized products, as well as C15/C16 and C17/C18 dioxidized products. Four new functionalized derivatives were prepared from the protected C17 oxidation product. C6 carboxylic acid, aldehyde, and normethyl derivatives were prepared from the C16 oxidation product. Many of these sequences were executed on gram scales. The efficiency and practicality of these routes provides an easy method to rapidly interrogate structure-activity relationships that were previously beyond reach. This study will inform the design of fully synthetic approaches to novel pleuromutilins and underscores the power of the hydroxyl-directed iridium-catalyzed C-H silylation reaction.
A Novel Anticancer Stem Cell Compound Derived from Pleuromutilin Induced Necroptosis of Melanoma Cells
Gao, Ruolin,Li, Ning,Li, Xuechun,Ma, Lan,Mu, Linrong,Song, Wei,Sun, Yue,Tang, Zhiwen,Wang, Ning,Wang, Ruonan,Wei, Mingming,Yang, Cheng,Yang, Guang,Yu, Xuan,Zhang, Kun,Zhang, Yan,Zheng, Nan
, p. 15825 - 15845 (2021/11/16)
Necroptosis has been recently confirmed as a non-apoptotic form of programmed cell death. Discovery of novel chemical entities, capable of inducing necroptosis of cancer cells, is likely to act as an alternative strategy for dealing with drug resistance clinically. In this study, the identification of a novel Pleuromutilin derivative (compound 38) is presented, capable of significantly increasing the cellular level of ROS and inducing melanoma cancer cell death via necroptosis. Furthermore, compound 38 noticeably ablated various cancer stem cells and inhibited the growth of melanoma cancer cells both in vitro and in vivo. Moreover, 38 exhibited low toxicity in animal models and excellent PK properties, which is currently being verified as a potential anticancer drug candidate.
COMPOUNDS THAT INDUCE FERROPTIC CELL DEATH
-
Page/Page column 50; 56; 67, (2020/10/21)
The diterpene natural product pleuromutilin was subjected to reaction sequences focused on creating ring system diversity in few synthetic steps. This effort resulted in a collection of compounds with previously unreported ring systems, providing a novel
