TETRAHEDRON LETTERS Tetrahedron Letters 44 (2003) 4823–4825 Pergamon Conversion of naringenin and hesperetin by heterogeneous catalytic Baeyer–Villiger reaction into lactones exhibiting apoptotic activity Roberta Bernini, a, * Enrico Mincione, a Manuela Cortese, a Raffaele Saladino, a Giampiero Gualandi b and Maria Cristina Belfiore b a Organic Chemistry, Dipartimento ABAC, Universita ` degli Studi della Tuscia, Via S. Camillo De Lellis, 01100 Viterbo, Italy b Genetic of Microorganisms, Dipartimento ABAC, Universita ` degli Studi della Tuscia, Via S. Camillo De Lellis, 01100 Viterbo, Italy Received 10 April 2003; revised 29 April 2003; accepted 3 May 2003 Abstract—Naringenin and hesperetin were converted into the corresponding lactones by hydrogen peroxide activated by poly(4-vinylpiridine)-supported methyltrioxorhenium in t -butanol, an environmentally friendly catalytic system. The products showed a marked apoptotic activity in the genetic tests. © 2003 Elsevier Science Ltd. All rights reserved. Among naturally occurring flavonoids, naringenin and hesperetin are very common in some edible fruits and vegetables as aglycons and glycosides. Naringenin is most abundant in grapefruit, 1 hesperetin in oranges, tangerines and lemons. 2 They occupy an important position in perfumery, cosmetic and in pharmaceutical formulations and hypocholesterolemic, 3 antiestrogenic, 4 hypolipidemic, 5 antihypertensive, 6 antiflammatory 7 activities have been reported. In a previous paper, we reported the Baeyer–Villiger rearrangement of some flavanones derivatives by the Methyltrioxorhenium (MTO)/Hydrogen Peroxide (H 2 O 2 ) system in homogeneous acidic conditions to get the corresponding lactones. 8 However, the methylated naringenin 3 and hesperetin 4 in these conditions reacted to give the quinones 5 and 6 as the only reaction products (Scheme 1, pathway a) as a conse- quence of the opening of the formed lactones to the corresponding phenols further oxidized to quinones by MTO. With the aim to develop an efficient and useful method to prepare these lactones which are reported to have many biological activities, 9 now we set up the conditions to operate the Baeyer–Villiger reaction in heterogeneous catalytic conditions, as well in a neutral solvent, using the MTO supported on poly(4- vinylpyridine) cross-linked with divinylbenzene 10 (Scheme 1, pathway b). We chose this matrix because pyridine beside being an acid buffer is also a good ligand of MTO. 11 Different reaction conditions as well as supports were experimented. As reported in Table 1, high conversions and satisfactory yields of lactones 9 and 10 were obtained without quinone formation. The same 5-methoxyflavanone 1 and 7-methoxyflavanones 2 gave the corresponding lactones 7 and 8. The demethyl- ation previously observed in homogeneous catalysis did not occur now. 8 Shorter reaction times, higher conversions of the substrates (90 and 88%) and better yields of 9 and 10 (80 and 72%) were observed with MTO supported on the poly(4-vinylpyridine) 25% cross-linked (PVP-25%/MTO, Table 1: entries 3 and 8), evidencing the influence of the morphologic characteris- tics of the polymeric support on the efficiency of the catalyst. In a typical experiment, to a suspension of 150 mg of the appropriate resin, prepared as reported, 10 in 5.0 ml of t -butanol, warmed at 80°C, were added the flavanone (0.3 mmol) and hydrogen peroxide H 2 O 2 (50% water solution). The reaction was monitored by thin layer chromatography. At the end of the experi- ment, the suspension was filtered. The recovered cata- lyst was washed with ethyl acetate and after drying under high vacuum it was efficiently used for three further runs of oxidation. After the removal of the Keywords : naringenin; hesperetin; Baeyer–Villiger reaction; heteroge- neous catalysis. * Corresponding author. Fax:+39(0)761357230; e-mail: berninir@ unitus.it 0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0040-4039(03)01139-0