02-060: Synthesis of Functionalized Gamma Carboline Derivatives

Researchers at George Mason University have formed a chemical sequence that provides for the building of functionalized Gamma-carboline derivatives, which have demonstrated antipsychotic, antibiotic, and antitumor activities.

Current methods of Gamma-carboline creation have limitations including low yields, are limited to nonfunctional substrates, involve extreme thermal conditions, or rely on specialty starting materials. The reported novel approach to the building of y-carbolines is capable of overcoming these limitations and may provide a new pathway for developing new medications to treat a variety of illnesses and disorders.
Gamma-Carbolines are involved in many biological processes and have been shown to possess various medicinal activities similar to those of beta-carboline. The pharmaceutical industry is interested in beta-carboline because of their close relationship with natural products such as tryptophan, an essential amino acid found in protein that plays a role in the production of serotonin (a neurotransmitter and hormone involved in the biochemistry of several diseases and conditions such as depression and anxiety). Beta-carboline, which are

found in plant, are structurally similar to neurotransmitters such as serotonin and dopamine.
The synthesis of functionalized gamma-carboline derivatives and their etrahydro precursors proceeds through the production of 3-aminomethyl indoles, which are not commercially available. The GMU researcher's discovery of a good 3-aminomethyl indole synthesis has allowed for the development of a novel synthetic approach to the creation of a large selection of functionalized gamma-carbolines. With this synthesis in place, they were able to develop a methodology that allows for control of the substitutents in the 1 and 4 positions of the Gamma-carboline system.

MarketSignificance:
Target industries for this invention are pharmaceutical and biomedical businesses. The described technology may aid researchers and drug developers in the creation of new drugs that may be used in a variety of applications including the development of new treatments for neurodegenerative diseases, as well as antipsychotic, antibiotic, antiviral, and antitumor preparations.

Advantages:
- Provides an efficient method of producing a large selection of highly functionalized gamma-carbolines synthetically
- Increases the ease of manipulation of gamma-carboline compounds
- Eliminates the need for specialty starting materials or extreme thermal conditions, common limitations to current methods of gamma-carboline creation
- Allows for the substitution of substituents in multiple, previously restricted positions of the compound
- Provides a new avenue for the possible development of novel antipsychotic, antibiotic, and antitumor drugs