Angewandte Chemie International Edition 2007, 46,
Natural Insecticide Re-Created in the Lab
Success after 22 years of research: synthesis of azadirachtin
Contact: Steven V. Ley, University of Cambridge (UK)
Registered journalists may download the original article here:
Synthesis of Azadirachtin: A Long but Successful Journey / A Relay Route for the Synthesis of Azadirachtin
Twenty-two years of dedicated research has finally resulted in success:
In the journal Angewandte Chemie, a British team headed by Steven
V. Ley at the University of Cambridge reports the first synthesis of
azadirachtin, a natural compound that stops predatory insects from
Plants have a variety of defense mechanisms to deter insect attack.
Investigation of these mechanisms often allows researchers to discover
molecules with interesting biological properties. One such compound is
azadirachtin, which was first isolated from the neem tree (also known as
the Indian lilac) in 1968. The name of this natural product is derived
from the botanical name of the plant, Azadiracta indica.
Azadirachtin is a highly active substance that inhibits the development
of the larvae of a broad spectrum of destructive insects but is harmless
to mammals and beneficial insects, such as bees and ladybugs.
The structure of this complicated molecule was published in 1985, after
a long, intensive research effort, but all attempts to make this
compound have thus far been unsuccessful. The difficulty of the
synthesis stems in part from the 16 stereocenters in the molecule, the
complex pattern of oxygen-containing functional groups, and a
conformation and reactivity that are strongly dependent on
intramolecular bridging hydrogen bonds. The compound is highly light
sensitive and can readily undergo structural rearrangement.
Ley and his team have been interested in solving the problem of the
synthesis of this compound for 22 years. Their endurance has now been
abundantly rewarded. The key steps in making this molecule involve a
Claisen rearrangement and a novel radical cyclization reaction.
“While we have been working on this complex synthesis,” says Ley, “we
have also developed a number of new methods that are of general use for
the construction of other important molecules.” Ley expects that using
the successful synthetic route will allow the development of simpler
derivatives of azadirachtin that are stable and may lead to a new
generation of environmentally acceptable insecticides.