Nav: Home

New synthetic route to potential medicines for type 2 diabetes

September 15, 2015

Aryl alkyl ethers are important structural motifs found in many biologically active compounds. Therefore, stereoselective etherification is a highly important synthetic operation in the preparation of drug candidates. However, very few enantioselective methods have been described for the synthesis of chiral tertiary aryl ethers.

Researchers at Toyohashi Tech have found that the SN2 reaction of α-chloro-β-keto esters with phenols proceeded smoothly despite the fact that the reaction occurred at a tertiary carbon [1]. They previously reported the highly enantioselective chlorination of β-keto esters with a chiral Lewis acid catalyst [2]. Thus, in the two investigations, they have successfully demonstrated the enantioselective phenoxylation of β-keto esters. The novel presented method allows the synthesis of α-aryloxy-β-keto esters with high enantioselectivity.

"Etherification by the SN2 reaction is an older synthetic method called Williamson ether synthesis, but very few researchers have succeeded in conducting this reaction with tertiary halides," said Associate Professor Kazutaka Shibatomi. "This is the first example of the enantioselective synthesis of α-aryloxy-β-keto esters, which would be useful synthetic intermediates for new drug candidates."

Using this method, the researchers demonstrated the synthesis of some biologically active compounds, such as a GPR119 agonist and a PPARγ modulator, for the potential treatment of type 2 diabetes. The researchers expect that the present method will also be helpful in preparing other types of synthetic drugs.
-end-
References:

[1] Kazutaka Shibatomi, Manato Kotozaki, Nozomi Sasaki, Ikuhide Fujisawa, and Seiji Iwasa (2015). Williamson ether synthesis with phenols at a tertiary stereogenic carbon: formal enantioselective phenoxylation of β-keto esters, Chemistry - A European Journal, Article published online before print, 10.1002/chem.201502042

[2] Kazutaka Shibatomi, Yoshinori Soga, Akira Narayama, Ikuhide Fujisawa, and Seiji Iwasa (2012). Highly enantioselective chlorination of β-keto esters and subsequent SN2 displacement of tertiary chlorides: a flexible method for the construction of quaternary stereogenic centers, Journal of the American Chemical Society, 134(24), 9836-9839, 10.1021/ja304806j

Further information

Toyohashi University of Technology
1-1 Hibarigaoka, Tempaku
Toyohashi, Aichi Prefecture, 441-8580, JAPAN
Inquiries: Committee for Public Relations
E-mail: press@office.tut.ac.jp

Toyohashi University of Technology, which was founded in 1976 as a National University of Japan, is a leading research institute in the fields of mechanical engineering, advanced electronics, information sciences, life sciences, and architecture.

Website: http://www.tut.ac.jp/english/

Toyohashi University of Technology

Related Diabetes Articles:

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
More Diabetes News and Diabetes Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...