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!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy