New chemical reaction aids drug manufacture

Tag : Nitrogen-Containing

Part of almost all the top 200 brand-name drugs is anitrogen-containing ring-shaped structure that chemists call an'N-heterocycle.' Manufacturing these drugs depends on the abilityto synthesise N-heterocycles, but most synthesis reactions take along time and produce toxic waste byproducts.
A University of Illinois at Chicago research group may have found afaster, cleaner, 'greener' way to streamline these chemicalreactions, and the National Institutes of Health has just awardedthe team a five-year, $1.48 million grant to prove itseffectiveness.
'Hopefully it will reduce the cost of doing business,' said TomDriver, assistant professor of chemistry, whose laboratory isleading the research effort. 'I can't compete with a pharmaceuticalcompany in inventing new materials, but what I can do is invent newtools for them to use. We're interested in making the synthesis ofdrugs a lot easier.'
Driver and his coworkers have devised a chemical reaction thatcreates a carbon-nitrogen bond, such as in the N-heterocycle, usingan azide, a chemical that powers the airbags in cars.
'You need a particular type of starting point that has to beenergetic, because the bonds we're trying to functionalise arequite stable,' he said. Since the azide contains three nitrogenatoms, he said, after it gives up one, 'the only byproduct in ourreaction is nitrogen gas, which is green and non-toxic.'
Driver's reaction reduces the number of steps needed to synthesisethe N-heterocycle molecules. He compares the process to a betterway of cooking a feast.
'You can do it using 15 to 20 pots and pans, which you've then gotto clean up. But if you can make that feast in a way that uses justone or two pots and pans, that would be fantastic.'
Driver's laboratory has already published four research papersdescribing the reaction.
'This is a brand new reaction - no one's ever done it before,' hesaid. 'We've demonstrated that what we're proposing works. Now,basically, we want to flesh it out in more detail and invent newreactions.'
The NIH is also interested in using Driver's reaction to altercertain chemotherapy drugs that cancer cells have developed a wayto pump out of themselves.
'We want to learn how to clog the pumps and turn them off,' Driversaid, so that standard chemotherapy drugs remain lethal to thecancer cells. A key obstacle is that 'between our blood and brain,these pumps exist as well,' which helps keep the chemotherapy drugsfrom being too neurotoxic.
Driver's team is trying to figure out how small molecules interactwith the pump, which scientists at pharmaceutical companies can usein designing chemotherapeutics.
'We're interested in mechanism,' said Driver. 'Our reaction can beemployed to ease the synthesis of these quite complex smallmolecules.
'We're not only going to be interested in the invention of newreactions, but also demonstrating its applicability in thesynthesis of complex functional, important small molecules.'

Source: University of Illinois at Chicago