Total synthesis and target identification of marine cyclopiane diterpenes

Tian Li, Shan Jiang, Yuanhao Dai, Xia Wu, Huihui Guo, Liang Shi, Xueli Sang, Li Ren, Jie Wang, Lili Shi, Wenming Zhou (), Houhua Li () and Hong-Dong Hao ()
Additional contact information
Tian Li: Northwest A&F University
Shan Jiang: Peking University
Yuanhao Dai: Northwest A&F University
Xia Wu: Peking University
Huihui Guo: Northwest A&F University
Liang Shi: Northwest A&F University
Xueli Sang: Northwest A&F University
Li Ren: Northwest A&F University
Jie Wang: Peking University
Lili Shi: Peking University Shenzhen Graduate School
Wenming Zhou: Northwest A&F University
Houhua Li: Peking University
Hong-Dong Hao: Northwest A&F University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Marine cyclopianes are a family of diterpenoid with novel carbon skeleton and diverse biological activities. Herein, we report our synthetic and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 (IRGM1) as a cellular target. Our asymmetric synthesis commences from Wieland-Miescher ketone and features a sequential intramolecular Pauson-Khand reaction and gold-catalyzed Nazarov cyclization to rapidly construct the 6-5-5-5 tetracyclic skeleton. The stereocontrolled cyclopentenone construction is further investigated on complex settings to demonstrate its synthetic utility. Furthermore, using an alkyne-tagged conidiogenone C-derived probe, IRGM1, a master regulator of type I interferon responses, is identified as a key cellular target of conidiogenone C responsible for its anti-inflammatory activity. Preliminary mechanism of action studies shows that conidiogenone C activates IRGM1-mediate dysfunctional mitochondria autophagy to maintain mitochondria quality control of inflammatory macrophages.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-55189-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55189-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-55189-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().