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!
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
25.04.2017 | Physics and Astronomy
25.04.2017 | Materials Sciences
25.04.2017 | Life Sciences