Promise For New Drug Development, An international team of scientists has devised a used method for making complex molecules. The reaction they have come up with ought to enable chemists to synthesize new varieties of a whole subclass of organic compounds called nitrogen-containing heterocycles, thus opening up new avenues for the development of novel pharmaceuticals and natural products ranging from chemotherapeutic compounds to bioactive plant materials such as morphine.
scientists:
"We think it is going to be a highly enabling reaction, not only for preparing complex natural products, but also for making pharmaceutical substances that include parts that were historicallyin the past challenging to make," Stoltz says. "This has suddenly made them simple to make, and it ought to permit medicinal chemists to access levels of complexity they could not historicallyin the past access."
specialized robotic tools in the Caltech Middle for Catalysis and Chemical Synthesis to find the optimal conditions and an appropriate catalyst to drive this particular type of reaction, known as an alkylation, because it adds an alkyl group (a group of carbon and hydrogen atoms) to the compound. The researchers describe the reaction in a recent advance online publication of a paper in Nature Chemistry.
The reaction creates compounds called heterocycles, which involve cyclic groups of carbon and nitrogen atoms. Such nitrogen-containing heterocycles are present in lots of natural products and pharmaceuticals, as well as in lots of synthetic polymers. In addition, the reaction manages to form carbon-carbon bonds at sites where a number of the carbon atoms are fundamentally hidden, or blocked, by larger nearby parts.
"Making carbon-carbon bonds is hard, but that is what they must make the complicated structures we are after," Stoltz says. "We're taking that up another notch by making carbon-carbon bonds in challenging scenarios. We are making carbon centers that have other carbon groups around them, and that is hard to do."
The huge majority of pharmaceuticals being made today do not include such congested carbon centers, Stoltz says - not a lot because they would not be effective compounds, but because they have been so difficult to make. "But now," he says, "we've made it simple to make those delayed centers, even in compounds that contain nitrogen. And that ought to give pharmaceutical companies new possibilities that they historicallyin the past could not think about."
Perhaps the most important feature of the reaction is that it yields 100 percent of version of its product. This is significant because lots of organic compounds exist in distinct versions, or enantiomers, each having the same chemical formula and bond structure as the other, but with functional groups in opposite positions in space, making them mirror images of each other. version can be thought of as right-handed, the other as left-handed.
The issue is that there is often a lock-and-key interaction between our bodies and the compounds that act on them - of the feasible hands of a compound can "shake hands" and fit appropriately. In fact, version will often have a beneficial effect on the body while the other will have a different and sometimes detrimental effect. Therefore, it is important to be able to selectively produce the compound with the desired handedness. For this reason, the FDA has increasingly necessary that the molecules in a specific drug be present in form.
