Chem Eur J Shanghai Institute of Medicine conducted re-research on the chemical composition of Meat Mushroom soft coral

The variety of corals and the abundance of secondary metabolites have always been the focus
of research by marine natural product scientists.
Twisted Sarchia Soft Coral is a widely studied type of Sarchia soft coral, the chemical composition of which has been studied since 1980
.
Professor Su Jingyu of Sun Yat-sen University and his colleagues discovered the first cispinedinedimer from twisted porphyllum soft corals collected from the South China Sea, which also marked the beginning
of chemical research on marine natural products in China.
Since then, a large number of cispinedine diterpenes and cispinedimers with a wide range of biological activity (cytotoxicity, protein tyrosine phosphatase 1B inhibitors, anti-inflammatory activity, etc.
) have been detected
from this species of soft coral.
Guo Yuewei's research group of Shanghai Institute of Materia Medica, Chinese Academy of Sciences has been committed to the research of Granaria lucidum soft corals since 2005, and so far, more than one-third of the 18 chemically studied Sarphyllum soft corals have been reported by the research group
.

Marine resources are abundant, but collection is relatively difficult, so marine natural products have the characteristics of
low content and difficult to replicate.
How to isolate marine natural products with novel structures more efficiently and quickly has always been an urgent scientific problem
.

On December 23, 2022, the team of Guo Yuewei of Shanghai Institute of Materia Medica, an international authoritative journal Chemistry-A European Journal Published online titled "Guided Isolation of An Uncommon Cembranoid Orthoester, Sarcotortin A, and Three Skeletal Diverse Terpenoids from the Hainan Soft Coral Sarcophyton tortuosum Based on Molecular.
" Networking Strategy", the team applied molecular networking strategy to chemically re-study a twisted Meat mushroom soft coral collected from Xiyao Island, Hainan, China, and found a series of compounds with novel structures and biological activity
.
The article was selected as a "Top 20% great Significance Paper"
by the magazine.

Fig.
1 Molecular network analysis of twisted Sarchid soft coral, compound 1-13

In recent years, molecular network strategies have been widely used in the discovery of natural products, which greatly improves the efficiency of
natural product isolation.
Inspired by this emerging technology, in order to further amplify the chemical diversity of the genus Sarphyllum lucidum and more efficiently isolate compounds worthy of in-depth pharmacological study, Guo's team applied molecular network strategies to chemically re-study
a twisted Sarphylum soft coral collected from Xiyao Island, Hainan, China.
Under the guidance of HPLC-HRMS/MS, the researchers analyzed the ether phase extract of twisted Sartoderma lucidum soft coral, and established several clusters
with similar structural fragments.
Then, based on their molecular weight and typical precursor ions, two desirable clusters
that may be diterpenoids and diterpene dimers are rapidly distinguished.
Finally, the researchers selected some nodes from the two clusters and quickly obtained a novel eunicellane-type diterpene with a primary ester fragment (1), an eunicellane-type diterpene with a rare spirocyclic butenolide fragment (2), two new cispinene diterpenes (7 and 8), and other related known terpenoids by conventional separation
.
Using spectroscopic data, X-ray diffraction analysis and/or quantum chemical calculations, the planar structure and stereoscopic
configuration of the new compound were determined.
All compounds were extensively screened for biological activity, with compound 7 having significant inhibitory properties for protein tyrosine phosphatase 1B, a promising drug target for the treatment of type 2 diabetes and obesity; Compounds 4 and 10 showed strong dose-dependent anti-inflammatory activity
against lipopolysaccharide-induced inflammation in RAW264.
7 macrophages.
In anti-tumor testing, compound 9 has some cytotoxicity
against 4 tumor cell lines (H1975, MDA-MB231, A549 and H1299).

Figure 2 Structural elucidation
of compound 1.
A.
1H-1H COSY, key HMBC and NOESY correlation
of compound 1.
B.
X-diffracted single crystals of compound 1

Among them, compound 1 is the first cispinedinediterpene
containing a primary ester group.
Natural products containing primary ester groups are relatively rare and mainly derived from land plants
.
They are mainly divided into four categories: regenane diterpene original ester, limonin original ester, steroid original ester, coumarin original ester
.
Only a few secondary metabolites containing primary ester groups have been found
from the sponge.
At the same time, the primary ester groups mentioned above exist as a functional substituent, and the primary ester group of 1 is part of the carbon skeleton, which is very rare
.
To explain the formation of 1, a possible biogenic pathway was proposed, which provides a reference
for further biosynthetic/total synthesis studies and pharmacological studies.

Figure 3 Biogenic pathway of compound 1

Researcher Guo Yuewei, researcher Li Jia and Dr.
Su Mingming, Shanghai Institute of Materia Medica, are the corresponding authors of the paper, and Chen Zihui, a 2018 doctoral student majoring in medicinal chemistry at Shanghai Institute of Materia Medica, is the first author
of the paper.
This work was supported
by the National Natural Science Foundation of China and the State Key Laboratory of New Drug Research of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences.

Full text link: https://doi.
org/10.
1002/chem.
202203487

Team introduction

Founded in 2000, Guo Yuewei's research group of Shanghai Institute of Materia Medica, has long been committed to the research of invertebrate chemistry, chemical ecology and biological activity/druggability in the South China Sea, especially in the field of chemical composition of soft corals in the South China Sea, and has achieved a series of research results
.
Top/leading publications in the field of chemistry such as Chem.
Rev.
(2012, 2015); Nat.
Prod.
Rep.
(2010, 2020, 2022),Angew.
Chem.
Int.
Ed.
(2020, 2021), APSB (2018), APS (2011, 2022), and Org.
Lett (2011, 2013, 2017, 2018, 2019, 2021) and other journals have been invited to publish a number of reviews and research papers, summarizing and reporting the important academic achievements of this group, as well as the insights and prospects of relevant development prospects and trends
in domestic and foreign fields.