Research

Greener Molecular Intermediates May Aid Drug Design

Rice University scientists further simplify method to make important precursor molecules


0610_LASZLO-1-WEB
By Mike Williams | July 05, 2017

Scientists at Rice University have simplified their approach to synthesize a highly versatile family of precursors en route to biologically active compounds. Their method should make drug design and development cheaper and more environmentally friendly.

Synthetic chemist László Kürti and postdoctoral researchers Zhiwei Ma and Zhe Zhou reported their synthesis of unprotected aziridine molecules, key building blocks in synthetic chemistry. The lab’s primary focus is to cut the number of steps it takes to synthesize nitrogen-containing chemical compounds. One way to do so is to simplify the synthesis of precursor molecules that can then be easily modified into products.

Their work appears in the Angewandte Chemie International Edition.

Aziridines are triangular structures containing two carbon atoms and a nitrogen atom that are interconnected. The energy content of aziridines is high due to the strain in the three-membered ring. This is the key to their usefulness as building blocks, since they can be opened readily when combined with suitable reaction partners, Kürti said.
Synthesizing aziridines that can be modified for the preparation of drugs and other industrial purposes usually involves steps to preserve the ability to functionalize their delicate nitrogen atoms, which are important to keep the products biologically active.

“The vast majority of research done in aziridine chemistry concerns only the syntheses of various protected aziridines, which often cannot be further functionalized,” Zhou said. “This simple method gives access to unprotected aziridines, which are much easier to functionalize.”

What’s the difference between protected and unprotected aziridines? “The key is the nitrogen atom,” he said. “When this nitrogen is connected to an electron-withdrawing group, the aziridine is protected, while connection to a hydrogen atom or alkyl groups gives rise to unprotected aziridines.”

The new method builds upon one introduced three years ago by Kürti and his colleagues and reported in Science. That paper described a way to make aziridines directly from olefin compounds in a single step and under mild conditions, but the transformation in some cases took days and left behind a toxic byproduct. (Olefins consist only of hydrogen and carbon atoms and are produced in huge quantities by the petroleum industry via the cracking of hydrocarbons.)

The new work streamlines the process and eliminates the toxicity, Kürti said. “We bring in a really cheap and readily available reagent, hydroxylamine O-sulfonic acid, and utilize it as an electrophilic nitrogen source for olefin aziridination reactions,” he said.

The advantages of the one-pot process include the ability to produce aziridines at room temperature in as little as a few hours and with a small amount of catalyst, he said. The only byproduct of the process is an environmentally benign and water-soluble sulfate.

The resulting molecules are also stereospecific, Zhou said. “Stereospecificity means that if one takes an olefin into a reaction with a strictly defined double-bond geometry (cis- or trans), that geometry will be fully preserved at the end of the process.”

Rice University, the National Institutes of Health, the National Science Foundation and the Robert A. Welch Foundation supported the research.




Social Posts

profile_image

Texas Children's Hospital

TexasChildrensHospital

Patients, families and staff of Texas Children's Cancer Center celebrated “Going Gold” for childhood cancer awareness with events this month at Texas Children's...

33 mins ago
profile_image

UTHealth

@UTHealth

RT @McGovernMed: September is #HealthAgingMonth https://t.co/lgfbyggUy7

34 mins ago
profile_image

UTHealth

@UTHealth

RT @McGovernMed: Clinical study to compare general anesthesia, sedation, in #stroke https://t.co/sETS9bOCaF

34 mins ago
profile_image

BCMHouston

@bcmhouston

RT @BCMHouston_News: Food allergy vs. food intolerance: @bcmhouston's @TCHFoodMD explains important distinction and the body's response: ht?

34 mins ago
profile_image

MD Anderson

@MDAndersonNews

How Pushpa Damle faced her fear of chemo to overcome #lungcancer: https://t.co/DS2LZfZDu0 #CancerMoonshot #LCSM? https://t.co/XjzS60lZHr

40 mins ago
profile_image

Rice University

@RiceUniversity

It's a beautiful day for a stroll through the @RiceFarmersMkt! https://t.co/LfzhxfXSUG

55 mins ago
profile_image

TAMU Health Sciences

@TAMHSC

Research shows that having a community recovery plan isn't as effective if there isn't public participation https://t.co/6MOuU2nsgC

1 hour ago
profile_image

Texas Children's Hospital

TexasChildrensHospital

Significant progress has been made inside Texas Children’s Legacy Tower! The 25-floor Legacy Tower will house 126 beds for pediatric and cardiovascular intensiv...

1 hour ago
profile_image

Rice University

@RiceUniversity

Check out the @ChaoCenter's Transnational Asia Speaker Series on Monday, Oct. 2! https://t.co/bmyZbroPwz

1 hour ago
profile_image

BCMHouston

@bcmhouston

RT @BCMHouston_News: .@bcmhouston receives renewal SPORE grant from @theNCI to continue advancing #lymphoma #immunotherapy research. https:?

1 hour ago
profile_image

Veterans Affairs

@DeptVetAffairs

Mobile pantry to serve Veterans at VA sites https://t.co/OM0FcvLQw1 via @tdtnews

1 hour ago
profile_image

UTHealth

@UTHealth

RT @tvparrot: Neat idea from @UTHealth ? Hurricane Harvey Heroes webpage highlights the unsung heroes in their hurricane approach. https://?

2 hours ago
profile_image

UTMB Health

@utmbhealth

#HealthTipTuesday: Take safety precautions to avoid injuries while doing repairs after #Harvey. Learn more:? https://t.co/FMwtIrOZdw

2 hours ago
profile_image

UTMB Health

UTMB.edu

Take safety precautions to avoid injuries while doing repairs after Hurricane Harvey. Learn more helpful recovery tips: https://www.utmb.edu/recovery

2 hours ago
profile_image

Baylor College of Medicine

BaylorCollegeOfMedicine

Baylor College of Medicine ranks among the healthiest 100 workplaces in the U.S.

2 hours ago