Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) are a significant problem in hospitals worldwide. Our group has worked with natural resources to find antimicrobial compounds effective against antibiotic-resistant bacteria. Stable quinone methide compounds have been isolated from various plants and have been shown to display interesting biological activities e.g. anti-virus, 1,2) antibiotic, 2-7) anti-malarial, 8,9) and anti-tumor [10][11][12] activities. Previously, we have reported the total synthesis and the anti-MRSA and anti-VRE activities of 12 variously oxidized natural abietanes 13,14) : 6,7-dehydroferruginol methyl ether, 15) ferruginol (1), [15][16][17] 11-hydroxy-12-oxo-7,9(11),13-abietatriene (2), 4) royleanone, 16) demethylcryptojaponol, 18) salvinolone, 19,20) sugiol methyl ether, 21,22) sugiol, 15,20,23) 5,6-dehydrosugiol methyl ether, 21,22) 5,6-dehydrosugiol, 13,22,24) 6b-hydroxyferruginol, 25) and taxodione (3) 13,17,26) via stereo-selective polyene cyclization. A quinone methide 2 (0.5-1 mg/ml of MIC) and taxodione 3 (4-10 mg/ml of MIC) showed potent activity against both MRSA and VRE among these series of compounds. As the quinone methide 2 was isolated from an east African medicinal plant (Plectranthus elegans) used as a remedy for intestinal worms, 4) serious human toxicity may be avoidable. We thus planed to synthesize 11-hydroxy-12-oxo-7,9(11),13-abietatriene 2 via an efficient route from industrially available dehydroabietic acid (4) in order to provide a larger amount of the sample for further investigations into biological activity and potential application. We propose to adopt the general name of abietaquinone methide for 11-hydroxy-12-oxo-7,9(11),13-abietatriene 2.In the previous total synthesis of abietaquinone methide 2, we performed ortho-oxidation of ferruginol 1 with dibenzoyl peroxide.14) Dibenzoyl peroxide is a well known initiator of polymer synthesis and an effective reagent for ortho-oxidation of phenols. However, industrial production of dibenzoyl peroxide was ceased in Japan. Although the various reactions of diacyl peroxides are well known, its application for organic synthesis had been quite limited because of its instability. R. H. Burnell reported the synthesis of 2 through an oxidation using benzeneseleninic anhydride. 27) In order to allow further investigation into the biological activities of quinone methide, e.g. anti-MRSA and anti-VRE activities, we planned to develop an efficient ortho-oxidation reaction of phenols using a stable and nontoxic reagent. We attempted oxidation of ferruginol with 2-iodoxybenzoic acid (IBX) 28,29) and iodobenzene diacetate, 30,31) obtaining a complex mixture without the expected 2. Treatment of ferruginol 1 with ceric ammonium nitrate (CAN) was also attempted, but 1 was not successfully oxidized to 2.Synthesis of mCBPO One of the most popular and stable commercially available peracids is meta-chloroperbenzoic acid (mCPBA 5). We are therefore interested in the reactiv...
