Synthesis of α,α-Difluorinated Phosphonate pSer/pThr Mimetics via Rhodium-Catalyzed Asymmetric Hydrogenation of β-Difluorophosphonomethyl α-(Acylamino)acrylates

Organic Letters
Hong-Xue ChenYong-Xiang Chen

Abstract

A novel and facile synthetic strategy for α,α-difluorinated phosphonate mimetics of phosphoserine/phosphothreonine utilizing rhodium-catalyzed asymmetric hydrogenation was developed. The dehydrogenated substrate β-difluorophosphonomethyl α-(acylamino)acrylates were first prepared from protected serine/threonine followed by asymmetric hydrogenation using the rhodium-DuPhos catalytic system to generate the chiral center(s). These important phosphonate building blocks were successfully incorporated into phosphatase-resistant peptides, which displayed similar inhibition to the 14-3-3 ζ protein as the parent pSer/pThr peptides.

References

Jul 13, 2000·Accounts of Chemical Research·M J Burk
Oct 4, 1996·The Journal of Organic Chemistry·Tsutomu YokomatsuShiroshi Shibuya
Aug 14, 2003·Chemical Reviews·Wenjun Tang, Xumu Zhang
Aug 21, 2003·Journal of the American Chemical Society·M Eugenio VázquezBarbara Imperiali
Apr 1, 2004·Journal of the American Chemical Society·Geoffrey J RoffNicholas J Turner
Jun 19, 2009·Nature·Matthew Thomson, Jeremy Gunawardena
Jul 24, 2010·Angewandte Chemie·Yong-Xiang ChenHerbert Waldmann
Jan 24, 2012·Nature Chemical Biology·Mary Katherine TarrantPhilip A Cole
Mar 17, 2012·The Journal of Organic Chemistry·Takashi KonnoShin-ichi Fukuzawa
Jun 26, 2012·Chemistry & Biology·Kaushik PanigrahiDavid B Berkowitz
Jun 26, 2012·Chemistry & Biology·Allison ArrendaleRichard F Borch
Feb 20, 2014·Frontiers in Genetics·Marina Uhart, Diego M Bustos
Feb 14, 2015·Gynecologic Oncology·Seiji MabuchiTomoyuki Sasano
Jun 2, 2015·Nature Chemical Biology·Daniel T RogersonJason W Chin
Jul 25, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Robert Roskoski
Mar 5, 2016·The Journal of Organic Chemistry·Qiao ChenRui Wang
Jun 24, 2016·Chemistry : a European Journal·Maria V IvanovaThomas Poisson
Apr 28, 2017·ACS Chemical Biology·Si-Yu ZhangYong-Xiang Chen
Sep 25, 2017·Chemical Communications : Chem Comm·Xi ChenMyongsoo Lee
Sep 26, 2017·Chemistry : a European Journal·Maria V IvanovaThomas Poisson

❮ Previous
Next ❯

Citations

Apr 17, 2020·Chemical Communications : Chem Comm·Bei-Bei HanYong-Xiang Chen

❮ Previous
Next ❯

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.