BEGIN:VCALENDAR VERSION:2.0 X-WR-CALNAME:EventsCalendar PRODID:-//hacksw/handcal//NONSGML v1.0//EN CALSCALE:GREGORIAN BEGIN:VTIMEZONE TZID:America/New_York LAST-MODIFIED:20240422T053451Z TZURL:https://www.tzurl.org/zoneinfo-outlook/America/New_York X-LIC-LOCATION:America/New_York BEGIN:DAYLIGHT TZNAME:EDT TZOFFSETFROM:-0500 TZOFFSETTO:-0400 DTSTART:19700308T020000 RRULE:FREQ=YEARLY;BYMONTH=3;BYDAY=2SU END:DAYLIGHT BEGIN:STANDARD TZNAME:EST TZOFFSETFROM:-0400 TZOFFSETTO:-0500 DTSTART:19701101T020000 RRULE:FREQ=YEARLY;BYMONTH=11;BYDAY=1SU END:STANDARD END:VTIMEZONE BEGIN:VEVENT CATEGORIES:College of Arts and Sciences,Thesis/Dissertations DESCRIPTION:Title: “Divergent Annulations and Applications of Imidazo-F used Azines and 2-Aminoimidazoles” Advisor: Dr. Sivappa Rasapalli, Che mistry & Biochemistry Dept., University of Massachusetts Dartmouth Committ ee Members: Dr. Catherine Neto, Chemistry & Biochemistry Dept., Universi ty of Massachusetts Dartmouth & Dr. Akbar Ali, Biochemistry and Molecula r Biotechnology Dept., UMass Chan Medical School Abstract: The 2-aminoim idazole (2-AI) motif is the structural core of the pyrrole-imidazole marin e alkaloids, including oroidin, sceptrin, and ageliferin. Its high polarit y, tautomeric instability, and crowded nitrogen framework make regioselect ive synthesis and late-stage modification difficult. Beyond natural produc ts, imidazoles and imidazo-fused azines are also common structural feature s in approved drugs and clinical candidates, adding practical motivation t o solve this synthetic problem. This dissertation proposes a synthetic platform built around a 2-aminopyri(mi)dine bearing a carbon-based reactiv e handle (imine, formimidine, acetamidine, guanidine, etc.). This handle e nables an ionic annulation through an ammonium ylide intermediate to form imidazo[1,2-a]azines. These bicyclic products are a stable, storable form of the target molecules, effectively a masked version of 2-aminoimidazoles . A Dimroth ring-opening reaction later releases the free, active 2-aminoi midazole on demand. Notably, the same carbon handle is shared across three distinct cyclization pathways, namely, ionic, radical-polar crossover (RP C), and hydrogen-atom-transfer (HAT). This dissertation work is divided in to three Chapters/Aims. Chapter/Aim 1 establishes the annulation pathways on azines such as pyrimidines and pyridines and defines their mechanistic limits. Chapter/Aim 2 applies the resulting building blocks to the synthes is of natural-product targets. The primary objectives are oroidin-type con geners, strepimidazoles, sceptrin, and ageliferin, while more ambitious ex tensions toward grossularines, dragmacidin cores, and ceratamine are pursu ed only after specific milestones are met. Chapter/Aim 3 evaluates matched pairs of fused and unmasked 2-AI compounds through three collaborative bi ological screening efforts: antibacterial and antibiofilm activity, anti-N aegleria fowleri activity with follow-up informed by the Arp2/3 pathway, a nd antifungal activity. Computational studies support all three aims as ne eded, guiding reaction design, helping distinguish between competing mecha nisms, modeling/designing the leads, and analyzing the structure-activity relationships. The expected outcome is a dissertation that unites mechanis tic methodology development, natural-product synthesis, and biological eva luation into a single coherent body of work.\nEvent page: https://www.umas sd.edu/events/cms/9-30-26-thesis-divergent-annulations-and-applications-of -imidazo-fused-azine.php X-ALT-DESC;FMTTYPE=text/html:

Title: “Divergent Annulatio ns and Applications of Imidazo-Fused Azines and 2-Aminoimidazoles”

Advisor: Dr. Sivappa Rasapalli\, Chemistry & Biochemistry Dept.\, Uni versity of Massachusetts Dartmouth

Committee Members: Dr. Cather ine Neto\, Chemistry & Biochemistry Dept.\, University of Massachusetts Da rtmouth & Dr. Akbar Ali\, Biochemistry and Molecular Biotechnology Dept. \, UMass Chan Medical School

Abstract: The 2-aminoimidazole (2-A I) motif is the structural core of the pyrrole-imidazole marine alkaloids\ , including oroidin\, sceptrin\, and ageliferin. Its high polarity\, tauto meric instability\, and crowded nitrogen framework make regioselective syn thesis and late-stage modification difficult. Beyond natural products\, im idazoles and imidazo-fused azines are also common structural features in a pproved drugs and clinical candidates\, adding practical motivation to sol ve this synthetic problem. This dissertation proposes a synthetic platf orm built around a 2-aminopyri(mi)dine bearing a carbon-based reactive han dle (imine\, formimidine\, acetamidine\, guanidine\, etc.). This handle en ables an ionic annulation through an ammonium ylide intermediate to form i midazo[1\,2-a]azines. These bicyclic products are a stable\, storable form of the target molecules\, effectively a masked version of 2-aminoimidazol es. A Dimroth ring-opening reaction later releases the free\, active 2-ami noimidazole on demand. Notably\, the same carbon handle is shared across t hree distinct cyclization pathways\, namely\, ionic\, radical-polar crosso ver (RPC)\, and hydrogen-atom-transfer (HAT). This dissertation work is di vided into three Chapters/Aims.

Chapter/Aim 1 establishes the annu lation pathways on azines such as pyrimidines and pyridines and defines th eir mechanistic limits. Chapter/Aim 2 applies the resulting building block s to the synthesis of natural-product targets. The primary objectives are oroidin-type congeners\, strepimidazoles\, sceptrin\, and ageliferin\, whi le more ambitious extensions toward grossularines\, dragmacidin cores\, an d ceratamine are pursued only after specific milestones are met. Chapter/A im 3 evaluates matched pairs of fused and unmasked 2-AI compounds through three collaborative biological screening efforts: antibacterial and antibi ofilm activity\, anti-Naegleria fowleri activity with follow-up informed b y the Arp2/3 pathway\, and antifungal activity. Computational studies supp ort all three aims as needed\, guiding reaction design\, helping distingui sh between competing mechanisms\, modeling/designing the leads\, and analy zing the structure-activity relationships. The expected outcome is a disse rtation that unites mechanistic methodology development\, natural-product synthesis\, and biological evaluation into a single coherent body of work.

Event page: http s://www.umassd.edu/events/cms/9-30-26-thesis-divergent-annulations-and-app lications-of-imidazo-fused-azine.php

DTSTAMP:20260922T212717 DTSTART;TZID=America/New_York:20260930T110000 DTEND;TZID=America/New_York:20260930T130000 LOCATION:Violette 210 SUMMARY;LANGUAGE=en-us:Divergent Annulations and Applications of Imidazo-Fu sed Azines and 2-Aminoimidazoles UID:1cfe6e8da272c1b73b89cf5230563675@www.umassd.edu END:VEVENT END:VCALENDAR