Synthesis of polyunsaturated fatty acid amides from the Zanthoxylum genus and halogen bond-catalysed Diels-Alder and Michael addition reactions

Abstract

Chapter 1: Bungeanools are natural alkamides that are isolated from the pericarps of Zanthoxylum bungeanum, commonly known as Sichuan pepper, and they are structurally like sanshools. These compounds can produce tingling/ numbing sensations when consumed, due to the presence of certain chemical structural moieties. Hydroxy-α-sanshool has been thoroughly studied biologically, however; in-depth research related to the bungeanools are limited. The yields of isolating such bungeanools from nature are generally low and tedious. Thus, in order to increase the availability of bungeanools, we have developed a not only stereoselective but flexible and practical synthetic route for bungeanool, isobungeanool, lanyuamide III and hazelamide from cheap and commercially available starting materials. Lastly, these bungeanools have an overall yield of around 20% in nine steps which is much higher than isolating these bungeanools from the Zanothoxylum pericarps. The key transformation step in the synthetic route was the stereoselective triphenylphosphone and phenol- catalysed isomerization of an alkynoate into its corresponding conjugated E-,E-dienoate. The four compounds- bungeanool, isobungeanool, lanyuamide III and hazelamide were synthesized successfully via this route, making these bungeanools more available for biological studies. Chapter 2 & 3: A 5-Iodo-1,2,3-triazolium cationic bidenate halogen bond catalyst has been strategically designed and synthesized successfully. The design of the catalyst consists of highly electronegative iodides, quaternarized triazolium core, and large bulky phenyl rings for the most optimum halogen bonding qualities. The catalyst was used to catalyse the Diels-Alder [4+2] cycloaddition successfully in high yields and low catalyst loading of only 1 mol%. 18 Diels-Alder adducts were successfully synthesized and isolated in relatively high yields and within a relatively short time period. Apart from being able to catalyse Diels-Alder reactions, this catalyst was also able to catalyse the Michael addition reaction, 17 adducts were successfully synthesized and isolated in relatively high yields and within a short time frame. In order to ensure that the catalyst’s activity is solely due to the halogen bond donor qualities, a series of control experiments were done to rule out hidden proton catalysis or radical mechanism. Gratifyingly, the catalysis observed for the two named reactions was indeed due to halogen bonding. Overall, a potent catalyst has been successfully designed and utilized to catalyse two named reactions and a series of examples were synthesized and isolated in high yields.