Presentation Title

Synthesis of Novel Bioactive Benzotriazole Derivatives by Gold Catalysis

Faculty Mentor

Robert Iafe

Start Date

23-11-2019 11:00 AM

End Date

23-11-2019 11:15 AM

Location

Markstein 205

Session

oral 2

Type of Presentation

Oral Talk

Subject Area

physical_mathematical_sciences

Abstract

Candida species cause a majority of superficial and disseminated fungal infections inhumans. In clinical settings there has been extensive documentation of developed resistance to triazole antifungals of several Candida species. The most commonly prescribed drug to combat fungal infections has extensive documentation of developedresistance to triazole antifungals. This has stimulated the need to develop new novel compounds with intriguing activities, broad biological spectra, and fewer adverse effects. A bioisostere of triazole is 1,2,3-benzotriazole (BT). A bioisostere is a compound with similar physical, chemical or biological properties. BT derivatives possess three sites available for hydrogen bonding and a larger conjugated system which allow pi-pi stacking interactions. It has been shown this variety of intermolecular interactions allows BT derivatives to bind with a diverse group of receptors of biological systems and could possess bioactivity to overcome triazole drug resistance. A series of 12 diarylmethane BT derivatives were synthesized containing the BT motif with potential bioactivity against the Candida species. The BT derivatives were synthesized in two steps starting from commercially inexpensive aldehydes. First, a Grignard reaction was performed using phenyl magnesium bromide and a substituted aldehyde to afford a diarylmethanol. Second, using a microwave-assisted gold-catalysis methodology developed in our lab, the benzylic alcohol was displaced with BT. The BT derivatives were characterized by proton nuclear magnetic resonance, carbon-13 magnetic resonance, infrared, and mass spectroscopy. Yields range from 60-98% with excellent regioselectivity (>95%) at the N1 position. In the future we plan to perform disk diffusion assays to establish the in-vitro minimum inhibitory concentration (MIC) against standard species of Candida.

Key Words: Organic Synthesis, Candida, Grignard, Gold Catalysis, Benzotriazole, Bioactivity

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Nov 23rd, 11:00 AM Nov 23rd, 11:15 AM

Synthesis of Novel Bioactive Benzotriazole Derivatives by Gold Catalysis

Markstein 205

Candida species cause a majority of superficial and disseminated fungal infections inhumans. In clinical settings there has been extensive documentation of developed resistance to triazole antifungals of several Candida species. The most commonly prescribed drug to combat fungal infections has extensive documentation of developedresistance to triazole antifungals. This has stimulated the need to develop new novel compounds with intriguing activities, broad biological spectra, and fewer adverse effects. A bioisostere of triazole is 1,2,3-benzotriazole (BT). A bioisostere is a compound with similar physical, chemical or biological properties. BT derivatives possess three sites available for hydrogen bonding and a larger conjugated system which allow pi-pi stacking interactions. It has been shown this variety of intermolecular interactions allows BT derivatives to bind with a diverse group of receptors of biological systems and could possess bioactivity to overcome triazole drug resistance. A series of 12 diarylmethane BT derivatives were synthesized containing the BT motif with potential bioactivity against the Candida species. The BT derivatives were synthesized in two steps starting from commercially inexpensive aldehydes. First, a Grignard reaction was performed using phenyl magnesium bromide and a substituted aldehyde to afford a diarylmethanol. Second, using a microwave-assisted gold-catalysis methodology developed in our lab, the benzylic alcohol was displaced with BT. The BT derivatives were characterized by proton nuclear magnetic resonance, carbon-13 magnetic resonance, infrared, and mass spectroscopy. Yields range from 60-98% with excellent regioselectivity (>95%) at the N1 position. In the future we plan to perform disk diffusion assays to establish the in-vitro minimum inhibitory concentration (MIC) against standard species of Candida.

Key Words: Organic Synthesis, Candida, Grignard, Gold Catalysis, Benzotriazole, Bioactivity