Technion advances ‘molecular architecture' theory

Discovery could speed development of new drugs and lead to large-scale reductions in pharmaceutical industry processes.

By JUDY SIEGEL-ITZKOVICH
Technion University (photo credit: Courtesy)
Technion University
(photo credit: Courtesy)
Technion-Israel Institute of Technology researchers announced a “breakthrough” that could lead to the speedy synthesis of new medications, in an article on their findings in the prestigious journal Nature.
Prof. Ilan Marek from the Technion’s chemistry department developed the novel approach to “molecular architecture” with his team of researchers.
“This is a significant scientific breakthrough that represents an effective solution to a major problem in organic synthesis that has never been resolved despite worldwide efforts, and could lead to large-scale reductions in pharmaceutical industry processes,” he said on Monday.
The Technion team successfully prepared a new molecular framework possessing a challenging asymmetric center in a single chemical step from easily available starting materials.
Until now, due to a lack of available efficient strategies, very few attempts were made, and they were all based on long and tedious approaches.
“This is a significant scientific breakthrough in synthesis that could lead to a considerable reduction in the production of pharmaceuticals,” Marek said.
For the development of original synthetic approaches, Marek received the prestigious Royal Society Chemistry Organometallic Award (2011) and last year the Janssen Pharmaceutica Prize for Creativity in Organic Synthesis.
“Synthetic organic synthesis is a science that deals with the building of complex organic molecules from simpler elements,” he explained.
“One of the greatest applications of this new approach is a quick and efficient synthesis of complex natural materials that may be used in the pharmaceutical industry.”
In the 21st century, Marek said, we must strive to accomplish more with less.
“In today’s society, no one can afford to follow the inefficient route of long and tedious synthesis. We should think about organic synthesis differently and I am sure that new transformations that were not possible to perform by conventional methods will soon appear,” he continued.
Although, there are still molecular frameworks that are extremely challenging to prepare, the real question of this new century is no longer “can we synthesize this molecule?” but rather “how can we synthesize it efficiently, using the fewest number of steps, with optimum convergence, with as little as possible functional group transformations, few or no byproducts and maximum atom efficiency and at minimal cost?” The Haifa-based research team has developed several innovative new synthetic methods that not only fulfill these requirements, but also give solutions to challenging problems in organic synthesis.
One of these critical challenges is the formation of “chiral all-carbon quaternary stereogenic centers in acyclic systems.” A chiral molecule is a type of molecule that has a non-superimposable mirror image. Human hands are perhaps the most universally recognized example of chirality – the left hand is a non-superimposable mirror image of the right hand; no matter how the two hands are oriented, it is impossible for all the major features of both hands to coincide.
This difference in symmetry becomes obvious if someone attempts to shake the right hand of a person using his left hand, or if a left-handed glove is placed on a right hand. This characteristic is also present in organic molecules, and two mirror images of a chiral molecule are called enantiomers.
Many biologically active molecules are chiral, including the naturally occurring amino acids (building blocks of proteins) and sugars. In biological systems, most of these compounds are of the same chirality, and understanding the origin of chirality may shed some light on the origin of life, the scientists said.
In many cases, both enantiomers of a specific material can affect the human body in completely different ways, and therefore understanding these chiral molecular characteristics is of great importance for the pharmaceutical and food industries.
The most infamous case of medical disaster was caused by a misunderstanding of the different pharmacological characteristics of two enantiomers of the same material, known as thalidomide, which caused severe birth defects including limbless infants. Thalidomide given to their mothers could interconvert the two enantiomers.
In the context of building molecules, the aldol reaction is one of the most versatile carbon-carbon bond formation processes available to synthetic chemists but also a critical biological reaction in the context of metabolism.
However, regarding efficiency, the “aldol reaction” (a powerful means of forming carbon-carbon bonds in organic chemistry) combines only two components with the creation of only one new carbon-carbon bond per chemical step. Better efficiency is now necessary in organic synthesis in which several new carbon-carbon bonds should be formed.