Optimization of the Synthesis of BNM-III-170 bis-TFA Salt

Loading...
Thumbnail Image
Penn collection
Master of Chemical Sciences Capstone Projects
Degree type
Discipline
Subject
Process Synthesis
BNM-III-170
HIV-1 entry inhibitor
small molecule CD4 mimetic compounds
ADCC
Chemistry
Funder
Grant number
Copyright date
Distributor
Related resources
Contributor
Abstract

There has been growing interest for small molecule CD4 mimetic compounds due to their capability to inhibit the HIV-1 entry and possibility to eradicate infected cells in livings. Certain experiments also prove that a lead compound, BNM-III-170 (+)-1, developed in the laboratory has direct antiviral effect and could sensitize HIV-infected cells toward Antibody-Dependent Cellular Cytotoxicity (ADCC). An efficient and scalable process synthesis for the HIV-1 entry inhibitor BNM-III-170 bis-TFA salt (+)-1 is described herein for further investigations. The synthesis employs a state-of-the-art dynamic-kinetic resolution (DKR) both to generate the stereogenicity and significantly reduce the number of chromatographic separations throughout the synthesis. By taking advantage of some modifications from the first-generation synthesis, along with the low solubility of late stage intermediate, the scale-up synthesis has been greatly improved from a few hundred milligrams in 6.2% yield over a 15- step sequence. Now to proceed on a 20-gram or larger scale in overall 16 steps and in 9.64% yield, requiring only one chromatographic separation.

Advisor
Date Range for Data Collection (Start Date)
Date Range for Data Collection (End Date)
Digital Object Identifier
Series name and number
Publication date
2020-05-05
Volume number
Issue number
Publisher
Publisher DOI
Journal Issue
Comments
Recommended citation
Collection