(S*)-2,7,8-Trihydroxychroman-4-one

Abstract

Reticumanone (1), a new chromanone, isolated from the leaves of Cinnamomum reticulatum Hay (Lauraceae), has been characterized as (S*)-2,7,8-trihydroxychroman-4-one, by means of spectroscopic methods.

1. Introduction

The Cinnamoum species (Lauraceae) have been used in folk medicine for sweating, antipyretic, and analgesic effect [1]. There is only one paper describing the constituents of Cinnamomum reticulatum Hay [1]. In the course of screening for biologically and chemically novel agents from Formosan Lauraceous plants [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17], C. reticulatum Hay was chosen for further phytochemical investigation. In this paper, we report the isolation and structural elucidation of this new chromanone compound (1).

2. Results and Discussion

Reticumanone (1), obtained as a white amorphous powder (CHCl₃), was assigned the molecular formula C₉H₈O₅ by HR-EIMS at m/z [M]⁺ 196.0374 (calcd for C₉H₈O₅, 196.0372). UV λ_max at 273, 310 (sh), 322 nm, IR bands at 1660 cm^-1 and a signal appearing at δ 182.4 in the ¹³C-NMR spectrum indicate the chromanone skeleton of this compound [18]. The IR spectrum revealed the presence of a hydroxyl group absorption at ν 3400 cm^-1. The ¹H-NMR spectrum of 1 showed one set of AB doublet signals at δ 6.81 (1H, d, J = 8.8), and 7.31 (1H, d, J = 8.8), one methine proton at δ 5.32 (1H, dd, J = 9.0, 3.4), and two methylene protons at δ 2.67 (1H, dd, J = 16.8, 9.0)/3.08 (1H, dd, J = 16.8, 3.4), indicating that 1 was probably a 2,7,8-trihydroxychroman-4-one. The ¹³C-NMR spectrum indicated that compound 1 had a total of 9 carbons, with the skeleton consisting of a chroman-4-one. The carbons of the chroman-4-one were assigned, from ¹³C-NMR and DEPT experiments, one methylene at δ 45.9 (C-3); three methines at δ 92.4 (C-2), 126.8 (C-6) and 131.4 (C-5); and five quaternary carbons at δ 111.8 (C-4a), 135.7 (C-8), 150.6 (C-8a), 152.1 (C-7) and 182.9 (C-4). The structure of 1 was also confirmed by 2D NMR experiments. A COSY correlation was observed between H-2 and H-3, and between H-5 and H-6 (Figure 1). The HETCOR experiment showed that the carbon signals at δ 92.4 for C-2, 45.9 for C-3, 131.4 for C-5 and 126.8 for C-6 were correlated to the proton signals at δ 5.32 for H-2, 2.67/3.08 for H-3, 7.31 for H-5 and 6.81 for H-6, respectively. The relative configuration of 1 was determined by 2D NOESY analysis. The observation of the NOESY correlation from H-3eq. to H-2 suggested that H-2 was in the β–configuration (Figure 2). Thus, the structure of 1 was determined to be (S*)-2,7,8-trihydroxychroman-4-one and has been named reticumanone.

3. Experimental

3.1. General

UV spectra were obtained on a Jasco UV-240 spectrophotometer in CH₃CN, IR spectra were measured on a Hitachi 260-30 spectrophotometer. ¹H NMR (400 MHz), HETCOR, HMBC, COSY, NOESY, and DEPT spectra were obtained on a Varian (Unity Plus) NMR spectrometer. Low-resolution EIMS spectra were collected on a Jeol JMS-SX/SX 102A mass spectrometer or Quattro GC/MS spectrometer having a direct inlet system. High-resolution EIMS spectrum was measured on a Jeol JMS-HX 110 mass spectrometer. Silica gel 60 (Merck, 70~230 mesh, 230~400 mesh) was used for column chromatography. Precoated Silica gel plates (Merck, Kieselgel 60 F-254), 0.20 mm and 0.50 mm, were used for analytical TLC and preparative TLC, respectively, visualized with 50% H₂SO₄.

3.2. Plant Material

The leaves of C. reticulatum Hay were collected from Pingtung County, Taiwan, May 2005. Plant material was identified by Professor Fu-Yuan Lu (Department of Forestry and Natural Resources College of Agriculture, National Chiayi University). A voucher specimen (Cinnamo. 6) was deposited in the School of Medical and Health Sciences, Fooyin University, Kaohsiung County, Taiwan.

3.3. Extraction and Isolation

The air-dried leaves of C. reticulatum Hay (3.4 kg) were extracted with n-hexane (30 L × 5) and CHCl₃ (30 L × 5) at room temperature and a n-hexane extract (43.5 g) and CHCl₃ extract (151.5 g) were obtained upon concentration under reduced pressure. The n-hexane extract (43.5 g) was chromatographed over silica gel (980 g, 70−230 mesh) using n-hexane/EtOAc/Acetone mixtures as eluents to produce five fractions. Part of fraction 4 (10.62 g) was subjected to silica gel chromatography by eluting with CHCl₃-MeOH (60:1), enriched with MeOH to furnish five further fractions (4-1−4-5). Fraction 4-2 (2.56 g) was further purified on a silica gel column using CHCl₃-MeOH mixtures to obtain reticumanone (4 mg).

Reticumanone ((S*)-2,7,8-trihydroxychroman-4-one) (1): White amorphous powder (CHCl₃); [α]²⁵_D–12.6° (c 0.005, CHCl₃); UV/Vis (CH₃CN): λ_max (log ε): 273 (3.62), 310 (sh), 322 (3.00) nm; IR (neat) ν_max: 3400 (br, OH), 2920, 2850, 1660 (C=O), 1250 cm^-1; MS (EI, 70 eV): m/z (%): 196 [M]⁺ (45), 179 (57), 163 (64), 147 (100), 90 (32); HR-MSEI: m/z [M]⁺ calcd for C₉H₈O₅: 196.0372; found: 196.0374; ¹H NMR (400 MHz, CDCl₃) δ 2.67 (1H, dd, J = 16.8, 9.0 Hz, H-3ax.), 3.08 (1H, dd, J = 16.8, 3.4 Hz, H-3eq.), 5.32 (1H, dd, J = 9.0, 3.4 Hz, H-2), 6.81 (1H, d, J = 8.8 Hz, H-6), 7.31 (1H, d, J = 8.8 Hz, H-5); ¹³C NMR (100 MHz, CDCl₃): 45.9 (C-3, CH₂), 92.4 (C-2, CH), 111.8 (C-4a, C), 126.8 (C-6, CH), 131.4 (C-5, CH), 135.7 (C-8, C), 150.6 (C-8a, C), 152.1 (C-7, C), 182.9 (C-4, C).