Asymmetric Total Synthesis and Biological Evaluation of the Natural PDE4 Inhibitor Toddacoumalone

被引：15

作者：

Hou, Ke-Qiang ^{[1
]}

Chen, Xue-Ping ^{[1
]}

Huang, Yiyou ^{[1
]}

Chan, Albert S. C. ^{[1
]}

Luo, Hai-Bin ^{[1
]}

Xiong, Xiao-Feng ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Guangzhou, Peoples R China

来源：

ORGANIC LETTERS | 2020年 / 22卷 / 02期

基金：

中国国家自然科学基金;

关键词：

DIELS-ALDER REACTIONS; 4+2 CYCLOADDITION; DESIGN; ALKYLATION; COUMARINS; CATALYSIS; DIENES;

D O I：

10.1021/acs.orglett.9b04355

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We describe herein the first asymmetric total synthesis and biological evaluation of the natural PDE4 inhibitor toddacoumalone and its stereoisomers. The key step of the total synthesis is a formal asymmetric [4 + 2] cycloaddition reaction catalyzed by chiral secondary amine catalysts. A variety of pyranoquinolinones and 3-methylcrotonaldehyde are well tolerated under the optimized reaction conditions, which paved the way for further SAR studies. Further biological evaluation showed 1a' with the best PDE4 inhibitory activity (IC50 = 0.18 mu M).

引用

页码：584 / 588

页数：5

共 50 条

[21] Synthesis and Biological Evaluation of 4a/4ß-Imidazolyl Podophyllotoxin Analogues as Antitumor Agents
Shang, Hai
Chen, Hong
Zhao, Dongmei
Tang, Xiaowei
Liu, Yongfeng
Pan, Li
Cheng, Maosheng
ARCHIV DER PHARMAZIE, 2012, 345 (01) : 43 - 48
[22] Asymmetric Synthesis of Highly Functionalized Tetrahydropyran DPP-4 Inhibitor
Xu, Feng
Zacuto, Michael J.
Kohmura, Yoshinori
Rosen, Jon
Gibb, Andrew
Alam, Mahbub
Scott, Jeremy
Tschaen, David
ORGANIC LETTERS, 2014, 16 (20) : 5422 - 5425
[23] Fe(III)-catalyzed regioselective and faster synthesis of isocoumarins with 3-oxoalkyl moiety at C-4: Identification of new inhibitors of PDE4
Thirupataiah, B.
Bhuktar, Harshavardhan
Mounika, Guntipally
Shukla, Sharda
Medishetti, Raghavender
Samarpita, Snigdha
Rasool, Mahaboobkhan
Jagadish, P. C.
Shenoy, Gautham G.
Pal, Manojit
Reddy, Gangireddy Sujeevan
Kumar, Jetta Sandeep
Hossain, Kazi Amirul
Parsa, Kishore V. L.
BIOORGANIC CHEMISTRY, 2022, 121
[24] Synthesis and biological evaluation of natural cleistanolate, its enantiomer and analogues
Kesic, Jelena
Popsavin, Mirjana
Benedekovic, Goran
Kojic, Vesna
Bosak, Anita
Matosevic, Ana
Farkas, Pavol
Madelova, Romana
Popsavin, Velimir
Kovacevic, Ivana
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2025, 287
[25] Total Synthesis of Orberryamides A, D and Their Biological Evaluation as Macrophage Differentiation Inhibitors
Ren, Tieshun
Lv, Ke
Ding, Ru
Hu, Fangzhong
Chen, Yue
JOURNAL OF ORGANIC CHEMISTRY, 2025, 90 (11): : 3888 - 3896
[26] Synthesis and preclinical evaluation of an 18F labeled PDE7 inhibitor for PET neuroimaging
Thomae, David
Servaes, Stijn
Vazquez, Naiara
Wyffels, Leonie
Dedeurwaerdere, Stefanie
Van der Veken, Pieter
Joossens, Jurgen
Augustyns, Koen
Stroobants, Sigrid
Staelens, Steven
NUCLEAR MEDICINE AND BIOLOGY, 2015, 42 (12) : 975 - 981
[27] Synthesis, Anti-inflammatory Activity and Docking Studies of Some Newer 1,3-Thiazolidine-2,4-dione Derivatives as Dual Inhibitors of PDE4 and PDE7
Sharma, Himanshu
Lather, Viney
Grewal, Ajmer Singh
Pandita, Deepti
CURRENT COMPUTER-AIDED DRUG DESIGN, 2019, 15 (03) : 225 - 234
[28] Asymmetric synthesis and biological evaluation of (+)-cardiobutanolide, (-)-3-deoxycardiobutanolide and analogues as antiproliferative agents
Kovacevic, Ivana
Kesic, Jelena
Popsavin, Mirjana
Francuz, Jovana
Kojic, Vesna
Jakimov, Dimitar
Rodic, Marko V.
Zelenovic, Bojana Sreco
Benedekovic, Goran
Popsavin, Velimir
TETRAHEDRON, 2021, 97
[29] FFPM, a PDE4 inhibitor, reverses learning and memory deficits in APP/PS1 transgenic mice via cAMP/PKA/CREB signaling and antiinflammatory effects
Guo, Haibiao
Cheng, Yufang
Wang, Canmao
Wu, Jingang
Zou, Zhengqiang
Niu, Bo
Yu, Hui
Wang, Haitao
Xu, Jiangping
NEUROPHARMACOLOGY, 2017, 116 : 260 - 269
[30] Efficient synthesis and biological evaluation of 4-arylcoumarin derivatives
Sun, Jie
Ding, Wei Xian
Zhang, Ke Yun
Zou, Yong
CHINESE CHEMICAL LETTERS, 2011, 22 (06) : 667 - 670

← 1 2 3 4 5 →