Nav: Home

New synthesis strategy for chiral drugs -- versatile chiral chemical species from aldehydes

January 09, 2019


Chirality is a geometric property of some molecules and ions, and a chiral molecule/ion is non-superposable on its mirror image, just like our right and left hands. A number of chiral molecules can be found in the world of chemistry, while their constituting atoms and alignment are the same. Enantiomers, which are chiral molecules, have similar chemical and physical characteristics but their biological functions, if any, are very different one another. For example, out of a pair of chiral molecules, one enantiomer may show an excellent pharmaceutical/medical activity while the other enantiomer may exert an adverse effect. Thus, developing a chemical synthesis reaction that selectively produces one enantiomer of chiral molecules useful in medicine is of great significance in the synthesis of drugs and their precursors.


Chiral hydroxycarbanions*1) are important in the asymmetric synthesis of chiral molecules. However, the conventional method for synthesizing a hydroxycarbanion requires a preparatory procedure consisting of multistep operations using metal reagents, the reactivity of which is difficult to control (Figure 1).

A research team at Kanazawa University has developed a new method of catalytic synthesis of chiral hydroxycarbanions from aldehydes and, by taking advantage of this, developed a new reaction protocol for asymmetric synthesis. More specifically, the group has designed a hybrid catalysis system consisting of a copper catalyst and a palladium catalyst in a synergistic manner, which enables the following processes, (i) and (ii) below, to take place in one flask while maintaining chirality information at the individual steps (Figure 1). As a ligand*2) for the copper catalyst, a newly designed chiral N-heterocyclic carbene*3) was found to be effective (Figure 2). It was revealed that this carbene plays important roles in catalytic activities, regulation of the reaction and enantioselectivity.

(i) A chiral copper species that is a chiral hydroxycarbanion equivalent is catalytically formed from an aldehyde through asymmetric silylation of the aldehyde and rearrangement reaction in a flask.

(ii) The chiral copper species thus formed in the flask is captured with an electrophile*4) in the presence of a palladium catalyst.

By the newly developed protocol, chiral biphenylmethanol that is an important basic structure in drugs such as anti-histamines and in drug candidate chemicals can be synthesized through the reaction of an aromatic aldehyde and a bromobenzene (Figure 3).

[Future prospect] Chiral hydroxycarbanion formation from an aldehyde developed in this study is highly versatile, being able to be captured by various electrophiles. That is, it has a high potential for a variety of asymmetric syntheses, previously thought to be next to impossible, of diverse chiral molecules. The new protocol is expected to pave the way to facilitation of syntheses of drugs and their candidate chemicals of complicated structure with chirality

*1) Carbanion
A carbanion is a chemical species in which carbon bears a negative charge.

*2) Ligand
A ligand is an organic molecule that binds to a central metal atom.

*3) Carbene
A carbene is a twofold coordination chemical species containing a neutral carbon atom with only six valence electrons.

*4) Electrophile
An electrophile is a chemical species that accepts an electron(s) in a chemical reaction.

Kanazawa 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

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at