Expanding diterpene complexity and diversity by photoinduced ring distortion

TIBALDI BOLLATI MARÍA LUZ; NICOTRA VIVIANA; GABRIELA OKSDATH; GARCÍA, MANUELA E.

Gante

Simposio; 22nd European Symposium on Organic Chemistry; 2023

Natural products (NPs) and their semi-synthetic derivatives are undoubtedly an important source of therapeutic agents. Their importance lies in their own origin and evolution; thus, they have a great chemical diversity, biochemical specificity and pharmacological properties.Currently there is a renewed interest in the development of methodologies capable of efficiently modifying the chemical structure of these bioactive platforms. Additionally, to afford highly distorted derivatives in few reaction steps and with few side products, the selection of a suitable methodology is a key point.In this sense, photochemistry provides a useful synthetic tool to be applied in the diversification of NPs, giving access to more complex structures that are often difficult to synthesize using other reaction types. Photochemical transformations can take place with high chemo-, region-, diastereo- as well as enantioselectivity. Moreover, these reactions can be performed at room temperature or using visible light (by the presence of a suitable photocatalyst), raising the possibility of developing greener processes. In this work, the photoderivatization of the diterpene solidagenone isolated from Solidago chilensis was explored using a complexity-to-diversity-oriented approach. By a straightforward and versatile methodology was feasible access to novel natural product-inspired compound classes was reported. To evaluate the structural diversity of the labdane derived compounds, their physicochemical properties, structural similarity, and chemical space were analyzed. These results suggest that photochemical reactions are a highly valuable tool for performing ring distortion transformation to afford derivatives of natural compounds with wide diversity and structural complexity. Finally, bioinformatics tools provide qualitative and quantitative information on the chemical properties of the diterpene derivatives, being particularly useful for prioritizing the compounds at the time of measuring their biological activity.