Antibacterial Novel Phenolic Diterpenes from Podocarpus macrophyllus D. DON

Abstract

and from the leaves of Podocarpus macrophyllus var. maki (Japanese name: Rakanmaki), norditerpenes and totarols having cytotoxic activities against P388 murine leukemia cells have been reported by us. [5][6][7] In the present study, from the bark of Podocarpus macrophyllus D. DON, we isolated 8 new diterpenes along with known ones. This paper describes the isolation and structural elucidation of these new diterpenes and their antibacterial activities against oral pathogenic microorganisms. Results and DiscussionBy sequential Diaion ® HP-20 column chromatography (H 2 O-MeOH) and silica gel column chromatography (CHCl 3 -MeOH) and the following repeated reversed-phase HPLC (MeCN-H 2 O, MeOH-H 2 O), a hot methanol extract of the bark of Podocarpus macrophyllus D. DON gave 8 new diterpene compounds (1-8) along with known lambertic acid (9), 8) 4b-carboxy-19-nortotarol (10), 8) totaradiol (11), 8) and macrophyllic acid (12). 9) Compound 1 was isolated as a colorless amorphous solid with [a] D ϩ262.6°(CHCl 3 ) and mp 124-126°C. The molecular formula was determined to be C 20 H 28 O 3 from the [M ϩ ϩNa] ion peak at m/z 339.1927 in HR-ESI-MS, implying the presence of 7 degrees of unsaturation. The IR absorption spectrum showed bands of carbonyl (1694 cm Ϫ1 ) and hydroxyl groups (3376 cm Ϫ1 ). The 1 H-and 13 C-NMR spectra of 1 (Table 1) . These data and the molecular formula suggested that 1 was an isomer of a known diterpene, 4b-carboxy-19-nortotarol (10) obtained also from this material. The heteronuclear multiple bond coherence (HMBC) correlations observed between the hydrogens H-15, H16, H-17 and the carbon C-12, and between the hydrogens H-14, H15, H-16 and the carbon C-13 indicated that the isopropyl group was at C-12 and the phenolic hydroxyl group at C-13. Further HMBC correlations between the hydrogens H-3 and H-18 and the carbonyl carbon C-19 showed that the carboxyl group was at C-4. The nuclear Overhauser effect (NOE)s between the methine proton H-5 and both the methyl protons H-18 and H-1a, respectively, and between the methyl protons H-20 and H-1b implied that the ring junction of A/B was trans and the stereochemistry of the methyl group attached to C-4 was a-oriented (Fig. 2). Hence, 1 was concluded to be 13-hydroxy-12-isopropyl-8,11,13-podocarpatrien-19-oic acid and was named inumakiol A. Only very few 12-isopropyl diterpenes are known and 1 was shown to be an analogue of such 12-isopropyl diterpene, sempervirol, 10) whose methyl group at C-4 is replaced by a carboxy group (Fig. 1).2 was isolated as a colorless amorphous solid with [a] D ϩ11.0°(CHCl 3 ) and mp 228-233°C. The molecular formula was determined to be C 20 H 28 O 3 from the [M ϩ ϩNa] ion peak at m/z 339.1895 in HR-ESI-MS, implying the presence of 7 degrees of unsaturation. The IR absorption spectrum showed bands of carbonyl (1646 cm Ϫ1 ) and hydroxyl groups (3432 cm Ϫ1 ). The 1 H-and 13 C-NMR spectra of 2 showed the presence of an isopropyl group [d C 28.5 (d), 22.7 (q), 22.6 (q) and d Table 1). The HMBC correlations observed between the hyd...

Two New Anti‐Proliferative C18‐Norditerpenes from the Roots of Podocarpus macrophyllus

“…[1] For instance, taxol, harringtonin, and camptothecin were identified from the Taxus, [2] Cephalotaxus, [3] and Camptotheca [4] species, respectively. Previously, a variety of flavonoids, [7] biflavonoids, diterpenoids (including norditerpenoid dilactones), [8] [9] and triterpenoids [10] have been reported from Podocarpus species. [5] There are thirteen species and three variants of Podocarpus in China.…”

“…[6] Some of them are widely used in traditional medicine for treatment of pain, fever, and rheumatism. Previously, a variety of flavonoids, [7] biflavonoids, diterpenoids (including norditerpenoid dilactones), [8] [9] and triterpenoids [10] have been reported from Podocarpus species. Among them, most diterpenoids exhibited various biological activities, such as antitumor, [11] antilipemic, [12] and anti-oxidation activities.…”

Coupling of Sterically Hindered Trisubstituted Olefins and Benzocyclobutenones by CC Activation: Total Synthesis and Structural Revision of Cycloinumakiol

“…Podocarpaceae1 is one of the most abundant evergreen trees distributed from Australia to the tropical and subtropical areas of Asia. Previous biological studies of the extracts from the leaves of this plant revealed high antibiotic as well as anticancer activities resulting from inumakiols,1a totarols,1b and other norditerpenes (Figure 1). 1c,d Recently, guided by a bioassay based on activator protein‐1 (AP‐1), the investigation on extracts of podocarpus latifolius at the National Cancer Institute (NCI) led to the isolation of three new inumakiol‐family diterpenes, namely cycloinumakiol ( 1 ), inumakal ( 2 ), and inumakoic acid ( 3 ) 2.…”

Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E

“…While the wood of this plant is used as timber for furniture and in paper-making, its edible fruits are consumed raw or cooked, and decoctions from its leaves are used in folk medicine to relieve rheumatism and painful joints [2]. Plants of the genus Podocarpus have been reported to exhibit a variety of biological activities ranging from plant-growth regulation [3, 4] to antibacterial [5] and antiproliferative [6–9] effects. These activities have been attributed mainly to their chemotaxonomic markers, the nor- and bisnorditerpene dilactones, referred to as the podolactones or nagilactones [10, 11].…”