Currently, the increase of food demand of a steadily growing human population is not balanced by a global agricultural supply. As a consequence, crop protection plays a crucial role in maximising crop productivity and preventing losses caused by biological and not biological agents. Biological agents, collectively named as pests, are responsible for quantitative losses ranging from 20 % to 40 %, and qualitative losses, thus reducing the value of crops. For these reasons, new methods to control pests must be developed.The discovery of new agrochemicals is necessary to face the problem of the emergence of resistances and the increasing of stringent regulatory standards, which are leading to the ban of many products no longer considered acceptable. All these factors are changing the research of new pesticides that is becoming a more expensive and time-consuming process. Thus, new methods to improve and speed up the discovery of new agrochemicals must be developed. In this context, the aim of this Ph.D. thesis was to explore new approaches to the synthesis of agrochemicals. Our attention was focused on the naturally derived compound-based molecules, due to the proved value of these compounds in development of agrochemicals and more in general of biologically active compounds. The first part of this Ph.D. thesis is focused on the development of dual-target fungicides obtained by combination of the naturally derived strobilurin fungicides with succinate dehydrogenase inhibitors. The development of dual-target molecules is a well-known approach in pharmaceutic research, while it is still underexplored in the field of agrochemicals. The research work was organized following a cycle of design, synthesis, in vitro tests, and evaluation of the mechanism of action. The dual-target compounds were designed on the basis of the reported structure-activity relationship for both the classes of fungicides. The designed compounds were synthetized, and the antifungal activity was screened in vitro by measurement of the mycelium growth inhibition. Finally, the mechanism of action was evaluated in silico by docking studies and in vitro in a cell free system. The second part of this dissertation was focused on the development of versatile synthetic approaches in the synthesis of biologically active natural compounds. SmI2 chemistry was employed in light of the remarkable synthetic power of this reagent. First, a SmI2-mediated Reformatsky reaction was developed as a complementary approach to Evans aldol reaction for the synthesis of precursors of cembranoids. Then, a SmI2-mediated pinacol coupling was investigated as a key step for the synthesis of the natural herbicide auscalitoxin aglycone.
|Titolo:||NEW APPROACHES IN THE DISCOVERY OF NATURAL PRODUCT-BASED AGROCHEMICALS|
|Supervisori e coordinatori interni:||BONOMI, FRANCESCO|
|Data di pubblicazione:||18-dic-2018|
|Parole Chiave:||agrochemicals; fungicides; dual-action compounds; succinate dehydrogenase inhibitors; strobilurins; samarium-Reformatsky; auscalitoxin|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Citazione:||NEW APPROACHES IN THE DISCOVERY OF NATURAL PRODUCT-BASED AGROCHEMICALS / M. Zuccolo ; tutor: S. Laschat ; tutor: S. Banfi. - Milano : Università degli studi di Milano. DIPARTIMENTO DI SCIENZE PER GLI ALIMENTI, LA NUTRIZIONE E L'AMBIENTE, 2018 Dec 18. ((31. ciclo, Anno Accademico 2018.|
|Appare nelle tipologie:||Tesi di dottorato|