New Approach to the Synthesis of 6-Geranylnaringenin via Ruthenium-Catalyzed Cross-Metathesis

Prenylated flavanones exhibit a broad spectrum of biological activities: neuroprotective, anti-cancerogenic, anti-fungal, anti-bacterial and estrogen-like activity as well as promotion of neuronal differentiation [1, 2]. Among C-6 and C-8 prenylated species, selective syntheses, especially for members bearing long terpene moieties, primarily exist for the C-8 prenylated flavanones. To examine the biological activities of C-6 substituted species, a synthetic approach providing access to the various C-6 substituted flavanones (e.g. prenyl, geranyl, farnesyl) was therefore designed.

Scheme 1: General reaction sequence for C-6 prenylated flavanones.

In this study, a method was designed, including cross-metathesis (CM) as key step and 6-allylnaringenin (6-AN, 2) [3] as general precursor (Scheme 1). This offers the benefit of a general synthesis instead of individual syntheses of desired C-6 prenylated flavonoids with different terpene moieties. Starting from naringenin (1), cross-metathesis between 6-AN (2) and 2,6-dimethyl-6-hepten-2-ol and subsequent dehydration of the tertiary alcohol promoted by BF₃·OEt₂ provided 6-geranylnaringenin (3) with a yield of 54%. A major advantage now is that olefins used for cross-metathesis can be varied broadly, thus opening a library of different natural products for screening.

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