(3R,4aR,5S,6R)‐6‐Hydroxy‐5‐methylramulosin: A New Ramulosin Derivative from a Marine‐Derived Sterile Mycelium.

Abstract

Marine microorganisms have attracted considerable attention as important sources of structurally diverse secondary metabolites and as potential leads for drug discovery. [1][2][3] In the course of our search for new biologically active compounds from marine-derived organisms, [4][5][6] we report here the isolation and structure elucidation of (3R,4aR,5S,6R)-6-hydroxy-5-methylramulosin (1), along with three known compounds, (Ϫ)-5-methylmellein (2), (Ϫ)-5-hydroxymethylmellein (3), and (Ϫ)-(3R,4R)-cis-4-hydroxy-5-methylmellein (4), which were isolated from Valsa ceratosperma, the pathogenic fungus of apple canker. 7) The marine-derived fungus was isolated from the green alga, Codium fragile (SURINGAR) HARIOT, collected in Toyama Bay in the Japan Sea. The fungus was grown on agar plates composed of 50% seawater with nutrients. The culture plates were extracted with EtOH. The extract was partitioned between EtOAc and H 2 O. The EtOAc-soluble fraction (4.5 g) was subjected to ordinary and reverse-phase silica gel column chromatography and HPLC to furnish 1 (16.0 mg), 2 (12.0 mg), 3 (26.0 mg), and 4 (3.6 mg).Compound 1 has a molecular formula of C 11 H 16 O 4 as established by HR-FAB-MS, and the molecular formula requires four degrees of unsaturation. The 1 H-NMR spectrum in CDCl 3 (Table 1) (Fig. 1). The heteronuclear multiplebond correlation (HMBC) experiment of 1 showed the correlations between H 2 -7 and two quaternary carbons C-8 (d 173.1) and C-8a (d 93.1) and between three hydrogens H-4b, H-4a, and H-5 and C-8a (Fig. 1). HMBCs were observed from H-3 to a carbonyl carbon C-1 (d 171.7) and from the downfield hydroxy resonance 8-OH to C-8 and C-8a, which clarified the connectivity of the quaternary carbons C-1, C-8, and C-8a. Thus, the planar structure of 1 was shown (Fig. 1). The relative stereochemistry of 1 was elucidated by its NOE experiment. NOE correlations between H-4a and two signals H-3 and H-6 indicated that they were oriented on the same side ( Fig. 1) at axial positions; hence the 3-Me and 6-OH groups were in equatorial orientation. While the correlations between 5-Me and two hydrogens H-4a (d 1.90) and H-7a (d 2.31) revealed that they were the opposite side of H-3, H4a, and H-6 and that they were in axial orientaion. The absolute stereochemistry of 1 was substantiated by applying the lactone sector rule by CD measurement, in which the signs, used in the ketone octant rule, are reversed for lactone sectors. 8) The sector projection, in which 1 is viewed in the plane of the lactone group along the line of the carboxyl group and its attached carbon atom, is shown in Fig. 2. The CD spectrum of 1 showed the positive Cotton effect observed at 260 nm (D eϭϩ126) due to the lactone group with the exocyclic a,b-double bond and with the b-hydroxy group bearing hydrogen bonding to the oxygen at C-1. As shown in Fig. 2, the positive contribution was exhibited for 1. Therefore, the structure of 1 was established as (3R,4aR,5S,6R)-6-hy-

First report of chromenyl derivatives from spineless marine cuttlefish Sepiella inermis : Prospective antihyperglycemic agents attenuate serine protease dipeptidyl peptidase‐IV

“…The antioxidant and antiinflammatory isochromenone and furanyl‐chromenyl metabolites were identified from estuarine mollusc, Paphia malabarica (Joy & Chakraborty, ) and bioactive hexahydro‐1 H ‐isochromenyl analogues were reported from Villorita cyprinoides (Joy & Chakraborty, ). Anticancerous hydrogenated chromenone was reported from marine‐derived mycelium of Codium fragile (El‐Beih, Kato, Ohta, & Tsukamoto, ) and 6‐hydroxy‐5‐methylramulosin from Camptotheca acuminate (Lin et al, ). The naturally derived chromenyl compounds with different pharmacologically active substituents have been vital for the development of nutraceutical and functional supplements.…”