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.
[1] E. Oberbauer, C. Urmann, C. Steffenhagen, L. Bieler, D. Brunner, T. Furtner, B. Bäumer, C. Bandtlow, S. Couillard-Despres, F. J. Rivera, H. Riepl, L. Aigner, J. Nutr. Biochem. 2013, 24, 1953-1962.
[2] Y. Wang, W. Tan, W. Z. Li, Y. Li, J. Nat. Prod. 2001, 64, 196-199.
[3] S. Tischer, P. Metz, Adv. Synth. Catal. 2007, 349, 147-151.[4] G. H. Posner, E. M. Shulman-Roskes, C. H. Oh, J.-C. Carry, J. V. Green, A. B. Clark, H. Dai, T. E. N. Anjeh, Tetrahedron Lett. 1991, 32, 6489-6492.