Master of Chemical Sciences Capstone Projects

Date of this Version

5-5-2020

Document Type

Capstone Report

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.

Keywords

Process Synthesis, BNM-III-170, HIV-1 entry inhibitor, small molecule CD4 mimetic compounds, ADCC

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Available for download on Thursday, November 05, 2020

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Date Posted:05 May 2020