Synthesis of spiro-tetrahydrothiopyran-oxindoles by Michael-aldol cascade reactions: discovery of potential P53-MDM2 inhibitors with good antitumor activity

Organic & Biomolecular Chemistry
Shengzheng WangChunquan Sheng

Abstract

Using proline as the catalyst, an organocatalytic Michael-aldol cascade reaction was developed for the synthesis of spiro-tetrahydrothiopyran oxindoles. The highly functionalized scaffold was assembled in moderate to good yields (51-78%) and excellent diastereoselectivities (>20 : 1 dr). Interestingly, the oxindoles displayed moderate to good in vitro antitumor activities and were validated as p53-MDM2 inhibitors, which represented promising lead compounds for antitumor drug discovery.

References

Jan 6, 2004·Science·Lyubomir T VassilevEmily A Liu
Jul 21, 2005·Journal of the American Chemical Society·Ke DingShaomeng Wang
Aug 12, 2006·The Journal of Organic Chemistry·Alexander DeitersStephen F Martin
Jan 17, 2007·Angewandte Chemie·Dieter EndersMatthias R M Hüttl
Sep 4, 2010·Science·Matthias RottmannThierry T Diagana
Dec 3, 2010·Nature Chemistry·Christoph GrondalDieter Enders
May 28, 2011·Chemical Reviews·Albert Moyano, Ramon Rios
Apr 11, 2012·Angewandte Chemie·Xuan ZhouYong Qin
May 15, 2012·Accounts of Chemical Research·Liang-Qiu LuWen-Jing Xiao
Aug 18, 2012·Chemical Society Reviews·Renato DalpozzoGiorgio Bencivenni
Feb 9, 2013·Chemical Communications : Chem Comm·Michail TsakosChristoforos G Kokotos
Jul 6, 2014·European Journal of Medicinal Chemistry·Bin YuHong-Min Liu
Aug 22, 2014·Chemical Reviews·Pankaj ChauhanDieter Enders
Mar 4, 2015·Journal of Medicinal Chemistry·Brett R BenoNicholas A Meanwell
Jun 25, 2016·Beilstein Journal of Organic Chemistry·Giorgos KoutoulogenisChristoforos G Kokotos
Sep 15, 2016·ACS Infectious Diseases·Na YeJia Zhou

❮ Previous
Next ❯

Methods Mentioned

BETA
column chromatography
X-ray
acylation
column

Software Mentioned

GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.