The aim of the thesis entitled “Synthesis and biological activity evaluation of natural products and their analogues” is to synthesize some natural products and their analogues in order to study SAR and evaluate their biological activity as fungicides or herbicides. The thesis reports the first enantioselective synthesis of crassinervic acid in 12 steps and 11.8% overall yield. Crassinervic acid, recently isolated from leaves of Piper crassinervium by Kato and co-workers, shows high antifungal activity mainly against Cladosporium cladosporioides and Cladosporium sphaerospermum (minimum amount required for the inhibition of fungal growth on TLC: 0.5 microg). Crucial steps for our synthetic strategy included an enantioselective Sharpless epoxidation of easily available geraniol, followed by a regioselective reduction of the corresponding epoxyalcohol, and a condensation of the monoterpene fragment with lithiated 4-hydroxymethylphenol. The successful coupling of the two moieties required an accurate choice of the protecting groups. On the basis of the developed strategy, the absolute configuration of the compound was assigned as (S). A short and efficient synthesis of racemic Crassinervic acid was also carried on and applied to the preparation of analogues. All the synthesized compounds were successively tested for antifungal activity and SAR studies were developed. Synthetic efforts towards Ascaulitoxin were also carried on. Ascaulitoxin, a new unusual phytotoxic bis-aminoacid N-glucoside, was isolated from the culture filtrate of Ascochyta caulina (P. Karst.) v.d. Aa and v. kest, the causal agent of leaf and stem necrosis of Chenopodium album (also known as lambsquarter or fat hen, a common world-wide weed of many arable crops such as sugar beet and maize), a promising microherbicide for the biological control of this common noxious weed. The proposed route is concise and modular, making it convenient for large scale preparation. Finally, an approach towards the synthesis of Harzianic acid was developed. This compound is a new antimicrobial antibiotic from a Trichoderma harzianum strain which was isolated for the first time in 1994 by Sawa et al.. Very recently Vinale et al., reported its isolation, absolute configuration and antifungal as well as plant growth promoting activity. Harzianic acid showed antifungal activity against Pythium irregulare, Sclerotinia sclerotiorum, and Rhizoctonia solani. The synthesis is now at a final stage.
|Titolo:||SYNTHESIS AND BIOLOGICAL ACTIVITY EVALUATION OF NATURAL PRODUCTS AND THEIR ANALOGUES|
|Supervisori e coordinatori interni:||SORLINI, CLAUDIA|
|Data di pubblicazione:||20-dic-2010|
|Parole Chiave:||antifungal ; enantioselective synthesis ; natural products ; herbicidal ; pesticides|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Citazione:||SYNTHESIS AND BIOLOGICAL ACTIVITY EVALUATION OF NATURAL PRODUCTS AND THEIR ANALOGUES ; tutor: Sabrina Dallavalle ; coordinatore: Claudia Sorlini. - Milano : Università degli studi di Milano. Università degli Studi di Milano, 2010 Dec 20. ((23. ciclo, Anno Accademico 2010.|
|Appare nelle tipologie:||Tesi di dottorato|