Terpenoid Conidiation Factors in Penicillium cyclopium

University dissertation from Bioorganic Chemistry, Lund University

Abstract: Filamentous fungi produce asexual dispersive spores (conidia), when conditions are not suitable for apical extension growth. Conidiation (the process by which conidia produced) in genus Penicillium has attracted considerable interest because of its wide usage in different areas. In addition, several Penicillium species are pathogenic toward humans and plants, causing crop spoilage as well as decay processes. It is consequently important to understand this process since it could provide tools to inhibit or to induce conidiation in the case when fungal conidia are harmful or are useful. However, the precise mechanism by which conidiation induction is triggered has proved to be elusive.

Recently, two fungal metabolites conidiagenol (1) and conidiagenone (2) were isolated from the fermentation broth of Penicillium cyclopium. They are related diterpenes, and show potent and selective conidiation inducing activity in liquid culture. 2 is believed to be the true inducer and 1 a biosynthetic precursor of 2, and its effect depends on its oxidation to 2 by the fungus.

In order to initiate a structure-activity relationship study, and to obtain analogues of the natural product with similar or more potent biological activity but more readily available, three types of analogues of conidiogenone 2 were prepared. Starting from the ring A which bears all the functional groups, the simplified ring A, ring AB and tricyclic analogues were designed and synthesized. They share the same functional groups as the parent molecular but differ in size. In addition, a reasonable route towards the total synthesis of conidiogenone (2) is proposed.

In the course of synthesis of the analogues, a mild method for hydrolysis of acetals in solvent-free conditions under microwave irradiation was developed, to meet the need for the selective deprotection of acetals.