Major
Chemistry
Research Abstract
DNA-damaging natural products, despite their promising activity, are often too toxic for clinical use as anti-cancer chemotherapies. Novel strategies to effectively modulate their cytotoxicity could expand the arsenal of usable drugs. Ficellomycin, a cytotoxic, DNA-alkylating antibiotic with a rare and unstable azabicyclo[3.1.0]hexane core, undergoes an intramolecular cyclization to render itself inert outside of a narrow pH range. Exploration of ficellomycin’s natural capacity for self-regulation may present a novel strategy for modulation of cytotoxicity more generally. Toward this end, we have synthesized a protected ficellomycin precursor in four steps and 6% overall yield. Key steps in the sequence include Sharpless asymmetric epoxidation, sodium azide based ring-opening, and Staudinger reduction.
Faculty Mentor/Advisor
Herman Nikolayevskiy
Included in
A Ficellomycin Inspired Platform: Modulating Cytotoxicity by Tuning the Instability of Substituted Azabicyclo[3.1.0]hexanes
DNA-damaging natural products, despite their promising activity, are often too toxic for clinical use as anti-cancer chemotherapies. Novel strategies to effectively modulate their cytotoxicity could expand the arsenal of usable drugs. Ficellomycin, a cytotoxic, DNA-alkylating antibiotic with a rare and unstable azabicyclo[3.1.0]hexane core, undergoes an intramolecular cyclization to render itself inert outside of a narrow pH range. Exploration of ficellomycin’s natural capacity for self-regulation may present a novel strategy for modulation of cytotoxicity more generally. Toward this end, we have synthesized a protected ficellomycin precursor in four steps and 6% overall yield. Key steps in the sequence include Sharpless asymmetric epoxidation, sodium azide based ring-opening, and Staudinger reduction.
