Technion advances ‘molecular architecture' theory
By JUDY SIEGEL-ITZKOVICH
Discovery could speed development of new drugs and lead to large-scale reductions in pharmaceutical industry processes.
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.
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
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
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.
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.