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Curcumin (CUR) is a natural compound that exhibits anti-inflammatory, anti-bacterial, and other biological properties. However, its application as an effective drug is problematic due to its poor oral bioavailability, solubility in water, and poor absorption from the gastrointestinal tract. The aim of this work is to synthesize monocarbonyl analogs of CUR based on the 9-methyl-9-azabicyclo[3.2.1]nonan-3-one (pseudopelletierine, granatanone) scaffold to improve its bioavailability. Granatane is a homologue of tropane, whose structure is present in numerous naturally occurring alkaloids, e.g., l-cocaine and l-scopolamine. In this study, ten new pseudopelletierine-derived monocarbonyl analogs of CUR were successfully synthesized and characterized by spectral methods and X-ray crystallography. Additionally, in vitro test of the cytotoxicity and anti-inflammatory properties of the synthesized compounds were performed.

Alkaloids compose a large class of natural products, and mono-methylated polyamines are a common intermediate in their biosynthesis. In order to evaluate the role of selectively methylated natural products, synthetic strategies are needed to prepare them. Here, N-methylcadaverine is prepared in 37.3% yield in three steps. The alternative literature two-step strategy resulted in reductive deamination to give N-methylpiperidine as determined by the single crystal structure. A straightforward strategy to obtain the mono-alkylated aliphatic diamine, cadaverine, which avoids potential side-reactions, is demonstrated.