GRANTED INVENTION PATENT

Technology Title: Simple Process for Obtaining Advanced Intermediates in the Preparation of Lipophilic Analogs of Gamma-Aminobutyric Acid (GABA) from Morita–Baylis–Hillman Adducts

Inventors:

Marcelo Gonçalves Montes D'Oca (Lattes CV)
Marieli Oliveira Rodrigues (Lattes CV)
Felipi Ramiro Sobral (Lattes CV)

Academic Unit: School of Chemistry and Food – EQA

Overview:
This invention describes a process for obtaining racemic forms of novel advanced intermediates of gamma-aminobutyric acid (GABA), specifically α-alkyl-substituted gamma-nitrohydroxyesters, via the Morita–Baylis–Hillman (MBH) reaction. The advanced intermediates proposed herein serve as synthetic precursors for lipophilic GABA analogs, which are currently used in the treatment of various neurodegenerative diseases associated with aging—such as Alzheimer’s, Parkinson’s, and Huntington’s diseases—as well as schizophrenia, epilepsy, anxiety, among others.
The α-alkyl-substituted gamma-nitrohydroxyesters are obtained in two steps with good yields, with the key step being the Morita–Baylis–Hillman reaction using substrates containing fatty chains of four to twenty-two carbon atoms (C4–C22), which may be linear, branched, saturated, unsaturated, or polyunsaturated.
This key step employs a low-cost, environmentally benign catalyst and commercially available, inexpensive reagents.
Furthermore, from these α-alkyl-substituted gamma-nitrohydroxyesters, α-alkyl-substituted hydroxy gamma-lactams—lipophilic GABA analogs—were successfully synthesized. These compounds provide a novel solution to the challenge of crossing the highly lipophilic Blood–Brain Barrier (BBB). They represent a viable alternative that reduces the need for high dosages of currently used compounds, thereby minimizing severe side effects, and open up a broad spectrum of potential technological and pharmacological applications.

Patent Status: Granted. PATENT LETTER NO. BR 10 2017 009769 2, issued on April 11, 2023.

Abstract: Available at this link.