Semi-Synthesis of Melodinine, Taberyunine, and Melosuavine Bis-Indole Alkaloids Through Chemical and Biological Methods

The first semi-synthesis of (-)-melodinine K was completed from the monoterpene indole alkaloid (-)-tabersonine through regioselective enzymatic hydroxylation and Polonovski-Potier coupling. Regioselective borylation strategies were used to achieve meta-oxygenated derivatives of (-)-tabersonine for analysis in a Drosophila fruit fly Alzheimer’s phenotype model. A library of oxygenated and epoxidized bis-indole alkaloid analogs in the taberyunine class were prepared to conduct a structure activity relationship (SAR) study of the bis-indole framework against colon cancer and melanoma cell lines. Alkaloid aryl trifluoroborates were synthesized to increase nucleophilicity of arenes for unfavored alpha-arylations of tertiary amines on route to melosuavine bis-indole alkaloids. Overall, nine new bis-indole alkaloids were synthesized in the melodinine, taberyunine, and melosuavine class that showed strong cytotoxicity against a variety of melanoma, colon cancer, and renal cancer cell lines.

Grantor dc:publisher

Temple University. Libraries

Year dc:date.issued

2022

Author dc:creator

• Gardner, Alexander Charles

Advisors dc:contributor.advisor

• Davis, Franklin A.
• Andrade, Rodrigo B.

Committee members dc:contributor.committeemember

• Wengryniuk, Sarah E.
• Sieburth, Scott McNeill
• Cannon, Kevin C.

• Organic chemistry
• Alkaloids
• Biotransformation
• Bis-indole
• Melodinine K
• Natural products
• Tabersonine

Statement dc:rights

• IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/20.500.12613/7731

OAI identifier oai:identifier

oai:scholarshare.temple.edu:20.500.12613/7731