Presentation Title

Method development for the synthesis of novel bis-5-alkylresorcinols

Faculty Mentor

Jeffrey Cannon

Start Date

18-11-2017 11:15 AM

End Date

18-11-2017 11:30 AM

Location

9-239

Session

Physical Sciences 4

Type of Presentation

Oral Talk

Subject Area

physical_mathematical_sciences

Abstract

Oncostemonols, a family of bis-5-alkylresorcinols initially isolated from Oncostemon bojerianum of the Madagascan rainforest, have demonstrated cytotoxicity towards the A2780 ovarian cancer cell line via the inhibition of DNA polymerase β. However, limited availability has hindered extensive biomedical research. We aimed to utilize two powerful transition metal – catalyzed coupling reactions to devise a method development for the efficient and modular synthesis of novel bis-5-alkylresorcinols from commercially available substrates. Utilizing these methods, we synthesized the majority of the natural products in high yield.

Summary of research results to be presented

Starting from phloroglucinol and undecanoic acid, both commercially available substrates, we were able to synthesize iodoresorcinol in 30+% yield and 11-bromo-undecene in 93% yield respectively. Utilizing developed optimized alkylation and acetylation methodology, we were able to synthesize the mono and dimethoxy iodoresorcinol derivative and the mono and diacetoxy iodoresorcinol derivative in 40+% yield, which is a very high yield as the maximum is 50%. Combining the base iodoresorcinol and its derivatives with the zinc bromides from the 11-bromo-undecene in palladium catalyzed Negishi cross couplings, we synthesized the Negishi coupled alkenyl-resorcinol products in ~70+% yield. With these synthons, we utilized Z-selective Grubbs cross-metathesis to synthesize 8 of the 12 naturally occurring oncostemonols with significantly higher yield than what plant isolation could provide. Through these methods, the remaining 4 natural products are easily within reach.

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Nov 18th, 11:15 AM Nov 18th, 11:30 AM

Method development for the synthesis of novel bis-5-alkylresorcinols

9-239

Oncostemonols, a family of bis-5-alkylresorcinols initially isolated from Oncostemon bojerianum of the Madagascan rainforest, have demonstrated cytotoxicity towards the A2780 ovarian cancer cell line via the inhibition of DNA polymerase β. However, limited availability has hindered extensive biomedical research. We aimed to utilize two powerful transition metal – catalyzed coupling reactions to devise a method development for the efficient and modular synthesis of novel bis-5-alkylresorcinols from commercially available substrates. Utilizing these methods, we synthesized the majority of the natural products in high yield.