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.

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.

- 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