Nerve damage from neurodegenerative disease and spinal cord injury has largely been considered irreversible, but Dartmouth researchers report progress in the effort to synthesize rare natural products that promote regeneration and growth of injured nerve cells.
Neurotrophins, or proteins that promote the development of neurons, have been investigated as potential therapeutic agents, but they have a variety of drawbacks. A group of small molecule natural products, however, possesses potent neurotrophic properties without some of the shortcomings of protein-based agents.
Unfortunately, a source of suitable quantities of these substances to enable thorough medicinal exploration has yet to be identified. As such, the development of synthetic processes to generate molecules in this class (and related unnatural analogs) is critically important to establish science capable of fueling the discovery of therapeutic agents within the class.
That said, many member of this natural product class boast very complex carbocyclic structures that have stood as substantial challenges to modern synthetic chemistry.
Now, Dartmouth researchers have discovered that one of their recently discovered chemical reactions is capable of delivering some of the most potent and rare members of this natural product class.
Their pursuits resulted in the laboratory preparation of three neurotrophic natural products in the class and demonstrated the first application of their new carbocycle-forming reaction in natural product synthesis.
In addition to these accomplishments, the researchers' study also led to the discovery of a new radical cascade reaction process that proved instrumental for completing their laboratory syntheses of these complex agents.
"Advances of this nature are critically important for defining a foundation of science necessary for advancing rare natural products as therapeutic agents," says co-author and principal investigator Glenn Micalizio, the New Hampshire Professor of Chemistry at Dartmouth College.
"Simply stated, without a synthetic means to access such agents, development of therapeutics based on their structure would not be possible. While other syntheses of natural products within this class have recently been reported by others, our current achievement defines a unique synthesis pathway that could be employed to prepare synthetic analogs not easily accessed by others. Also, this marks the first successful application of our chemical method for hydrindane synthesis in the context of natural product synthesis."
The findings appear in the Journal of the American Chemical Society. A PDF is available on request.
The research was supported by the National Institutes of Health.
Professor Glenn Micalizio is available to comment at Glenn.C.Micalizio@dartmouth.edu.
Broadcast studios: Dartmouth has TV and radio studios available for interviews. For more information, visit: http://communications.
John Cramer | EurekAlert!
Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel
The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
23.01.2017 | Health and Medicine
23.01.2017 | Physics and Astronomy
23.01.2017 | Process Engineering