Cargando…

Unprecedented sesterterpenoids, orientanoids A–C: discovery, bioinspired total synthesis and antitumor immunity

Sesterterpenoids are a very rare class of important natural products. Three new skeletal spiro sesterterpenoids, named orientanoids A–C (1–3), were isolated from Hedyosmum orientale. Their structures were determined by a combination of spectroscopic data, X-ray crystallography, and total synthesis....

Descripción completa

Detalles Bibliográficos
Autores principales: Zheng, Cheng-Yu, Zhao, Jin-Xin, Yuan, Chang-Hao, Peng, Xia, Geng, Meiyu, Ai, Jing, Fan, Yao-Yue, Yue, Jian-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685275/
https://www.ncbi.nlm.nih.gov/pubmed/38033907
http://dx.doi.org/10.1039/d3sc04238c
_version_ 1785151594837311488
author Zheng, Cheng-Yu
Zhao, Jin-Xin
Yuan, Chang-Hao
Peng, Xia
Geng, Meiyu
Ai, Jing
Fan, Yao-Yue
Yue, Jian-Min
author_facet Zheng, Cheng-Yu
Zhao, Jin-Xin
Yuan, Chang-Hao
Peng, Xia
Geng, Meiyu
Ai, Jing
Fan, Yao-Yue
Yue, Jian-Min
author_sort Zheng, Cheng-Yu
collection PubMed
description Sesterterpenoids are a very rare class of important natural products. Three new skeletal spiro sesterterpenoids, named orientanoids A–C (1–3), were isolated from Hedyosmum orientale. Their structures were determined by a combination of spectroscopic data, X-ray crystallography, and total synthesis. To obtain adequate materials for biological research, the bioinspired total syntheses of 1–3 were effectively achieved in 7–8 steps in overall yields of 2.3–6.4% from the commercially available santonin without using any protecting groups. In addition, this work also revised the stereochemistry of hedyosumins B (6) and C (10) as 11R-configuration. Tumor-associated macrophages (TAMs) have emerged as important therapeutic targets in cancer therapy. The in-depth biological evaluation revealed that these sesterterpenoids antagonized the protumoral and immunosuppressive functional phenotype of macrophages in vitro. Among them, the most potent and major compound 1 inhibited protumoral M2-like macrophages and activated cytotoxic CD8(+) T cells, and consequently inhibited tumor growth in vivo.
format Online
Article
Text
id pubmed-10685275
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher The Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-106852752023-11-30 Unprecedented sesterterpenoids, orientanoids A–C: discovery, bioinspired total synthesis and antitumor immunity Zheng, Cheng-Yu Zhao, Jin-Xin Yuan, Chang-Hao Peng, Xia Geng, Meiyu Ai, Jing Fan, Yao-Yue Yue, Jian-Min Chem Sci Chemistry Sesterterpenoids are a very rare class of important natural products. Three new skeletal spiro sesterterpenoids, named orientanoids A–C (1–3), were isolated from Hedyosmum orientale. Their structures were determined by a combination of spectroscopic data, X-ray crystallography, and total synthesis. To obtain adequate materials for biological research, the bioinspired total syntheses of 1–3 were effectively achieved in 7–8 steps in overall yields of 2.3–6.4% from the commercially available santonin without using any protecting groups. In addition, this work also revised the stereochemistry of hedyosumins B (6) and C (10) as 11R-configuration. Tumor-associated macrophages (TAMs) have emerged as important therapeutic targets in cancer therapy. The in-depth biological evaluation revealed that these sesterterpenoids antagonized the protumoral and immunosuppressive functional phenotype of macrophages in vitro. Among them, the most potent and major compound 1 inhibited protumoral M2-like macrophages and activated cytotoxic CD8(+) T cells, and consequently inhibited tumor growth in vivo. The Royal Society of Chemistry 2023-11-06 /pmc/articles/PMC10685275/ /pubmed/38033907 http://dx.doi.org/10.1039/d3sc04238c Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Zheng, Cheng-Yu
Zhao, Jin-Xin
Yuan, Chang-Hao
Peng, Xia
Geng, Meiyu
Ai, Jing
Fan, Yao-Yue
Yue, Jian-Min
Unprecedented sesterterpenoids, orientanoids A–C: discovery, bioinspired total synthesis and antitumor immunity
title Unprecedented sesterterpenoids, orientanoids A–C: discovery, bioinspired total synthesis and antitumor immunity
title_full Unprecedented sesterterpenoids, orientanoids A–C: discovery, bioinspired total synthesis and antitumor immunity
title_fullStr Unprecedented sesterterpenoids, orientanoids A–C: discovery, bioinspired total synthesis and antitumor immunity
title_full_unstemmed Unprecedented sesterterpenoids, orientanoids A–C: discovery, bioinspired total synthesis and antitumor immunity
title_short Unprecedented sesterterpenoids, orientanoids A–C: discovery, bioinspired total synthesis and antitumor immunity
title_sort unprecedented sesterterpenoids, orientanoids a–c: discovery, bioinspired total synthesis and antitumor immunity
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685275/
https://www.ncbi.nlm.nih.gov/pubmed/38033907
http://dx.doi.org/10.1039/d3sc04238c
work_keys_str_mv AT zhengchengyu unprecedentedsesterterpenoidsorientanoidsacdiscoverybioinspiredtotalsynthesisandantitumorimmunity
AT zhaojinxin unprecedentedsesterterpenoidsorientanoidsacdiscoverybioinspiredtotalsynthesisandantitumorimmunity
AT yuanchanghao unprecedentedsesterterpenoidsorientanoidsacdiscoverybioinspiredtotalsynthesisandantitumorimmunity
AT pengxia unprecedentedsesterterpenoidsorientanoidsacdiscoverybioinspiredtotalsynthesisandantitumorimmunity
AT gengmeiyu unprecedentedsesterterpenoidsorientanoidsacdiscoverybioinspiredtotalsynthesisandantitumorimmunity
AT aijing unprecedentedsesterterpenoidsorientanoidsacdiscoverybioinspiredtotalsynthesisandantitumorimmunity
AT fanyaoyue unprecedentedsesterterpenoidsorientanoidsacdiscoverybioinspiredtotalsynthesisandantitumorimmunity
AT yuejianmin unprecedentedsesterterpenoidsorientanoidsacdiscoverybioinspiredtotalsynthesisandantitumorimmunity