The development of methods for site-selective derivatization of natural products to enable simultaneous arming and structure activity relationship (SAR) studies has shown great potential for the synthesis of pharmaceutical drug leads and cellular probes for mechanism of action studies. Herein, we describe a strategy to functionalize carboxylic acid and phenol containing natural products. This methodology relies on the in situ generation of diazoalkanes to form the corresponding carbonyl esters and phenolic ethers derived from natural products. We applied this process to several natural products, to begin demonstrating the utility of this methodology for the simultaneous arming and SAR studies of natural products.
To expand our group’s nucleophile catalyzed aldol lactonization (NCAL) reaction for synthesizing highly substituted cyclopentane fused beta-lactones, we developed a nucleophile catalyzed, tandem Michael aldol lactonization (NCMAL) reaction. Herein, we show the synthetic utility of this reaction in varying the Michael donors and acceptors, developing a catalytic, enantioselective NCMAL, and synthesizing tricyclic-!-lactones. Furthermore, we initiated studies toward applying this new methodology to the synthesis of a lipase inhibitor, vibralactone.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/149474 |
| Date | 03 October 2013 |
| Creators | McFarlin, Rae |
| Contributors | Romo, Daniel, Begley, Tadhg, Singleton, Daniel, Straight, Paul |
| Source Sets | Texas A and M University |
| Language | English |
| Detected Language | English |
| Type | Thesis, text |
| Format | application/pdf |
Page generated in 0.0019 seconds