Title

Diastereoselectivity in an Exhaustive Bromination of an Anthracenyl-Isoxazole

Presentation Type

Poster

Abstract

The focus of this project is to improve the efficacy of anthracenyl isoxazolyl amides (AIMs) by adding axial chirality via strategic halogenation. AIMs are a novel class of antitumor agents specially synthesized to bind and interact with G-quadruplex (G4) DNA; binding G4 DNA has been shown to repress the replication of oncogenes in cancerous tumors. By using asymmetric halogenation our goal is to create an axially chiral molecule, that is a molecule divided by a bond, or axis, that cannot freely rotate due to steric hindrance. Many biologically active molecules are chiral and the stereoisomers often display a significant difference in activity due to interactions with chiral targets, such as DNA. Methods of over halogenation of unsubstituted anthracenes, in synthetically useful yields, have been published by Cakmak. However, with the added complexity of a substituted anthracene, the addition of halogens has been a challenge. We have successfully isolated a 1,2,3,4,10-pentabromo-anthracenyl-isoxazole-ethylester. The methods that yielded the overbrominated product require consideration of the mechanism of the reactions, in which ionic and radical intermediates are expected to predominate. The current focus is the selective reductive elimination of the overbrominated compound. The future focus will shift to selective substitution that will afford an axially chiral final product. The benefit of stereospecific activity is that a patient may be able to take less of the chemotherapeutic agent and achieve equally beneficial results with fewer side effects. Our progress will be described.

Category

Physical Sciences

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Apr 17th, 11:00 AM Apr 17th, 12:00 PM

Diastereoselectivity in an Exhaustive Bromination of an Anthracenyl-Isoxazole

South UC Ballroom

The focus of this project is to improve the efficacy of anthracenyl isoxazolyl amides (AIMs) by adding axial chirality via strategic halogenation. AIMs are a novel class of antitumor agents specially synthesized to bind and interact with G-quadruplex (G4) DNA; binding G4 DNA has been shown to repress the replication of oncogenes in cancerous tumors. By using asymmetric halogenation our goal is to create an axially chiral molecule, that is a molecule divided by a bond, or axis, that cannot freely rotate due to steric hindrance. Many biologically active molecules are chiral and the stereoisomers often display a significant difference in activity due to interactions with chiral targets, such as DNA. Methods of over halogenation of unsubstituted anthracenes, in synthetically useful yields, have been published by Cakmak. However, with the added complexity of a substituted anthracene, the addition of halogens has been a challenge. We have successfully isolated a 1,2,3,4,10-pentabromo-anthracenyl-isoxazole-ethylester. The methods that yielded the overbrominated product require consideration of the mechanism of the reactions, in which ionic and radical intermediates are expected to predominate. The current focus is the selective reductive elimination of the overbrominated compound. The future focus will shift to selective substitution that will afford an axially chiral final product. The benefit of stereospecific activity is that a patient may be able to take less of the chemotherapeutic agent and achieve equally beneficial results with fewer side effects. Our progress will be described.