Curcumin has received attention due to its unique pharmacological properties, e.g. anti- inflammatory, antioxidant, anti-bacterial, and chemotherapeutic. The natural source of curcumin provides a mixture of curcumin and curcuminoids with variable composition, which complicates the correct assessment of biological properties. Curcumin consists of an extended conjugated system with a hydroxy and methoxy functional groups on the aromatic ring. Modification of the aromatic substituents leads to a class of compound known as curcuminoids. These substances are proposed to potentially exceed the pharmacological potency of curcumin. The synthesis adopted by the pharmaceutical industry is specific to curcumin and is not efficient in isolation of a series of analogs. Herein we report our hybrid synthetic/computational exploration of approaches towards this class of compounds. Starting aldehydes with varied electron density on the oxygen atoms of the extended conjugation using electron withdrawing and electron donating substituents on aromatic rings were applied. The effect of relative orientation of substituents in ortho-, meta-, and para-positions was investigated. Comprehensive variation of experimental parameters, e.g. reaction temperature, time, isolation method, was investigated. Attempts to explain the observed synthetic trends, e.g. product’s yields and distribution, with structure of starting aldehydes were supported by theoretical calculation of electron density of starting materials. Aldehydes were optimized at the B3LYP/6-31G** level of theory. The identified trends demonstrate an interesting mismatch based on the traditionally proposed mechanism of the reaction. Collected 11B nuclear magnetic resonance spectra for reaction mixtures and isolated intermediates are used in support of our hypothesis. Our preliminary findings indicate that the structure of isolated curcuminoids is highly dependent on the details of the synthetic approach. This information potentially could shed additional light on further investigation of the biological properties of this class of compounds by the scientific community.

Hybrid synthetic-computational study of versatile approach to curcuminoids

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.