CHAMPAIGN, Ill. - The synthesis of both left- and right-handed versions (enantiomers) of alpha-, beta- and gamma- (aryl) amino acids is the latest application of a new chemical methodology developed by a chemist at the University of Illinois.
"The importance of both natural and unnatural amino acids to medicinal and biological chemistry has made these compounds a focal point for chemical synthesis," said Peter Beak, a U. of I. professor of chemistry. "We have demonstrated that our methodology will produce both enantiomers of three types of aryl amino acids more efficiently and more conveniently than conventional techniques."
Amino acids like many organic molecules exhibit a particular "handedness," or chirality. The two resulting structures, called enantiomers, are analogous to a pair of hands: They form nonsuperimposable mirror images of each other. The reactions of chiral compounds are highly structure dependent, just as the right hand of one person requires the right hand of another to perform a handshake. Thus, the correct chirality must be built into a synthesized biomolecule.
"Our chemistry begins with a molecule that is superimposable on its mirror image, and converts it into an aryl amino acid that is nonsuperimposable on its mirror image," Beak said. "Our yields are high, depending upon the reagent being used and the type of amino acid being produced."
Beak's methodology, developed in collaboration with Yong Sun Park, a postdoctoral research associate, uses a process of transient molecular bonding called chiral ligand binding. In this synthetic approach, an auxiliary molecule the ligand binds to a lithium ion, which is associated with an amine derivative present in the solution, to make a complex. Because the ligand is chiral, it also imparts the correct "handedness" to subsequent reactions.
"The key to our technique is the association between the lithium ion and the chiral ligand in a critical step," Beak said. "By carrying out the lithiation and substitution in the presence of the chiral ligand and selecting the appropriate reagents, we are able to generate a product that is highly enriched in either of the two enantiomers of the desired amino acid."
The production of unnatural amino acids is of particular interest to the pharmaceutical industry, Beak said. "Nature uses only one enantiomer of amino acids in the construction of enzymes and proteins. The metabolism of the human body has developed ways to break these down. By placing an unnatural amino acid in biologically active molecules, the stability of a possible drug can be significantly enhanced."
In addition to synthesizing enantiomers of aryl amino acids, Beak also
has used his chiral ligand chemistry to create a variety of enantioenriched
acids, amides, amines and aldehydes. Beak's latest research results were
published in the March 21 issue of the Journal of Organic Chemistry.