NATURAL PRODUCT AND BUILDING BLOCK SYNTHESIS: CAROLACTON-INSPIRED ANALOGS, THE ANTITUMOR THERAPEUTIC FRAX-1036, AND THE CONSTRUCTION OF ATOMICALLY PRECISE MEMBRANES FROM SPIROLIGOMERS

Ever since traditional medicine developed thousands of years ago, humans have looked to natural substances as remedies for maladies. Today, many isolation and natural product chemists have begun revisiting ancient folk medicines in an attempt to isolate the compound(s) responsible for effective treatment. In addition to the examination of traditional remedies, the secondary metabolites of many newly discovered species, especially bacteria, get tested against a wide array of pathogenic cells. Isolated from the myxobacterium Sorangium cellulosum, the secondary metabolite carolacton was discovered to be lethal to Streptococcus mutans cells transitioning to the biofilm state. This was a significant finding since S. mutans is the main causative agent of dental caries, the most prevalent chronic childhood and adolescent disease worldwide. Herein, our efforts to design, synthesize, and biologically evaluate a 16-member library of carolacton-inspired analogs is described. In addition to natural product inspired research, two projects borne from a target-oriented templated approach are also described. The first, the synthesis of the antitumor compound FRAX-1036, was completed as part of a collaboration with the Chernoff group at Fox Chase Cancer Center to provide them with more material for murine testing. The second, the synthesis of macrocycles for the formation of atomically precise membranes, was conducted using spiroligomer building blocks and unnatural amino acids to furnish a triangle-shaped macrocycle via solution and solid phase techniques. This dissertation highlights the usefulness of the techniques of diverted total synthesis and building block synthesis in organic chemistry.

Grantor dc:publisher

Temple University. Libraries

Year dc:date.issued

2019

Author dc:creator

• Koval, Alex

Advisor dc:contributor.advisor

• Schafmeister, Christian

Committee members dc:contributor.committeemember

• Wang, Rongsheng
• Sieburth, Scott McNeill
• Cannon, Kevin C.

• Chemistry, Organic
• Biofilm
• Building block
• Carolacton
• Frax
• Spiroligomer

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/20.500.12613/3140

OAI identifier oai:identifier

oai:scholarshare.temple.edu:20.500.12613/3140