Nav: Home

A nice reactive ring to it: New synthetic pathways for diverse aromatic compounds

November 27, 2019

Researchers at the Tokyo Medical and Dental University (TMDU) discover a new method for synthesizing γ-aryl-β-ketoesters, an important class of molecules for the pharmaceutical industry

Tokyo, Japan - Researchers at the Tokyo Medical and Dental University (TMDU) have introduced a new synthetic process for producing an important family of carbon-based molecules known as γ-aryl-β-ketoesters. These molecules are used in the production of many vital pharmaceuticals, including alectinib, which is administered to treat non-small-cell lung cancer, and Januvia, a diabetes drug. This chemical approach may help in the preparation of a diverse range of their analogs and many other medication candidates more quickly.

Organic chemistry, which studies reactions involving carbon-based molecules, is central to the pharmaceutical industry. Certain reactions, such as the formation of multi-substituted aromatic compounds, are essential to the production of a variety of drugs. One important class of molecules that can be utilized as versatile intermediates are the γ-aryl-β-ketoesters. However, it was difficult to synthesize a variety of these critical molecules. In a study published in Organic Letters at October 24, researchers from Tokyo Medical and Dental University (TMDU) report a new reaction pathway to easily produce γ-aryl-β-ketoesters. To do this, they utilized aryne chemistry, which involves the removal of two substituents from a benzene ring, yielding a very reactive chemical species. "To successfully synthesize the γ-aryl-β-ketoesters, we decided to use a pathway that involves γ-aryl-β-ketoester-type arynes, because they are useful intermediates for creating multi-substituted aromatic derivatives," says first author Keisuke Uchida.

As a demonstration of the value of producing γ-aryl-β-ketoester using this novel method, the research team synthesized an analog of alectinib, which is an important inhibitor of certain lung cancers. As a complex molecule, the synthesis of various analogs by the conventional method takes considerable time and efforts, so the new approach that renders various γ-aryl-β-ketoesters easily available can improve the accessibility to them. This is true for many other organic compounds as well. "By virtue of the flexibility of aryne intermediates, our new synthetic approach may assist in the preparation of many important bioactive compounds, both for the pharmaceutical sector as well as for agrochemical sciences," senior author Takamitsu Hosoya says. The research group plans to expand the scope of their method to other molecules which may lead to faster and more cost-effective drug discovery in the future.
-end-
The article "Synthesis of Diverse γ-Aryl-β-ketoesters via Aryne Intermediates Generated by C-C Bond Cleavage" was published in Organic Letters at DOI: 10.1021/acs.orglett.9b03418

Tokyo Medical and Dental University

Related Molecules Articles:

How molecules self-assemble into superstructures
Most technical functional units are built bit by bit according to a well-designed construction plan.
Breaking down stubborn molecules
Seawater is more than just saltwater. The ocean is a veritable soup of chemicals.
Shaping the rings of molecules
Canadian chemists discover a natural process to control the shape of 'macrocycles,' molecules of large rings of atoms, for use in pharmaceuticals and electronics.
The mysterious movement of water molecules
Water is all around us and essential for life. Nevertheless, research into its behaviour at the atomic level -- above all how it interacts with surfaces -- is thin on the ground.
Spectroscopy: A fine sense for molecules
Scientists at the Laboratory for Attosecond Physics have developed a unique laser technology for the analysis of the molecular composition of biological samples.
Looking at the good vibes of molecules
Label-free dynamic detection of biomolecules is a major challenge in live-cell microscopy.
Colliding molecules and antiparticles
A study by Marcos Barp and Felipe Arretche from Brazil published in EPJ D shows a model of the interaction between positrons and simple molecules that is in good agreement with experimental results.
Discovery of periodic tables for molecules
Scientists at Tokyo Institute of Technology (Tokyo Tech) develop tables similar to the periodic table of elements but for molecules.
New method for imaging biological molecules
Researchers at Karolinska Institutet in Sweden have, together with colleagues from Aalto University in Finland, developed a new method for creating images of molecules in cells or tissue samples.
How two water molecules dance together
Researchers have gained new insights into how water molecules interact.
More Molecules News and Molecules Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 3: Shared Immunity
More than a million people have caught Covid-19, and tens of thousands have died. But thousands more have survived and recovered. A week or so ago (aka, what feels like ten years in corona time) producer Molly Webster learned that many of those survivors possess a kind of superpower: antibodies trained to fight the virus. Not only that, they might be able to pass this power on to the people who are sick with corona, and still in the fight. Today we have the story of an experimental treatment that's popping up all over the country: convalescent plasma transfusion, a century-old procedure that some say may become one of our best weapons against this devastating, new disease.   If you have recovered from Covid-19 and want to donate plasma, national and local donation registries are gearing up to collect blood.  To sign up with the American Red Cross, a national organization that works in local communities, head here.  To find out more about the The National COVID-19 Convalescent Plasma Project, which we spoke about in our episode, including information on clinical trials or plasma donation projects in your community, go here.  And if you are in the greater New York City area, and want to donate convalescent plasma, head over to the New York Blood Center to sign up. Or, register with specific NYC hospitals here.   If you are sick with Covid-19, and are interested in participating in a clinical trial, or are looking for a plasma donor match, check in with your local hospital, university, or blood center for more; you can also find more information on trials at The National COVID-19 Convalescent Plasma Project. And lastly, Tatiana Prowell's tweet that tipped us off is here. This episode was reported by Molly Webster and produced by Pat Walters. Special thanks to Drs. Evan Bloch and Tim Byun, as well as the Albert Einstein College of Medicine.  Support Radiolab today at Radiolab.org/donate.