Synthesis and photodecomposition of antibiotics containing ethanolamine and oxazolidine moieties.

Abstract

Abstract Antimicrobial resistance is a leading cause of death globally and is on the rise. The discovery of new antibiotics is declining, and the synthesis of new scaffolds with decomposing properties is more important now than ever to combat the rise of antimicrobial resistance. The goal of this project was to synthesize photodecomposable antibiotics containing the ethanolamine moiety, and further modify this to the corresponding oxazolidine. 1-((2,5-Dichloro-4-nitrophenyl)amino)-3-phenylpropan-2-ol (3a) was successfully synthesized to a yield of 13%. Compound 3a was used to synthesize 5-benzyl-3-(2,5-dichloro-4- nitrophenyl)oxazolidine (4) in a yield of 31%. Photodecomposition was conducted for compounds 3a and 4, and they were fully photodecomposed after approximately 24 hours as judged by 1H NMR. Compounds 3a and 4 have been submitted for biological testing and results are expected later this spring. Results from biological testing are therefore not included in this report. Attempts were also made to synthesize 1-((2,6-dichloro-4-nitrophenyl)amino)-3- phenylpropan-2-ol (3b) using the appropriate aniline (1b) and (2,3-epoxypropyl)benzene (2). None of the reactions that were attempted were successful.

Abstract Antimicrobial resistance is a leading cause of death globally and is on the rise. The discovery of new antibiotics is declining, and the synthesis of new scaffolds with decomposing properties is more important now than ever to combat the rise of antimicrobial resistance. The goal of this project was to synthesize photodecomposable antibiotics containing the ethanolamine moiety, and further modify this to the corresponding oxazolidine. 1-((2,5-Dichloro-4-nitrophenyl)amino)-3-phenylpropan-2-ol (3a) was successfully synthesized to a yield of 13%. Compound 3a was used to synthesize 5-benzyl-3-(2,5-dichloro-4- nitrophenyl)oxazolidine (4) in a yield of 31%. Photodecomposition was conducted for compounds 3a and 4, and they were fully photodecomposed after approximately 24 hours as judged by 1H NMR. Compounds 3a and 4 have been submitted for biological testing and results are expected later this spring. Results from biological testing are therefore not included in this report. Attempts were also made to synthesize 1-((2,6-dichloro-4-nitrophenyl)amino)-3- phenylpropan-2-ol (3b) using the appropriate aniline (1b) and (2,3-epoxypropyl)benzene (2). None of the reactions that were attempted were successful.