Three New Diterpenoids from the Leaves ofThuja orientalis

Abstract

Three new diterpenoids, 18-formyloxy-8β-hydroxysandaracopimar-15-ene (1), 15(R)-n-butoxypinusolidic acid (2), and 15,16-dihydro-15,16-dimethoxylambertianic acid (3), along with twelve known compounds (4-15) were isolated from MeOH extracts of leaves of Thuja orientalis L. The structures of the three new compounds were elucidated on the basis of spectroscopic analyses, including extensive 2D-NMR data. The absolute stereochemistry of compound 2 was clarified by a CD spectroscopic study. The isolated compounds were evaluated for cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines in vitro using the sulforhodamin B (SRB) bioassay.

Two New Diterpenoids from Thuja orientalis and Their Cytotoxicity

“…Previously, 3 was reported with incomplete stereochemistry, 6 and now we reported the complete stereostructure of 3. Compounds 1, 2 and 4-9 were evaluated for their cytotoxicity against A549 (non small cell lung adenocarcinoma), SK-OV-3 (ovarian cancer cells), A498 (renal cell carcinoma) and HCT-15 (colon cancer cells) human tumor cell lines using an in vitro sulforhodamine B (SRB) assay.…”

“…The planar structure of 1 was confirmed by the DEPT, The NOESY cross-peaks of H-12a/H-9, H-16 and H-17b and H-11/H-14 showed the same orientation for H-12a, H-16 and H-17b ( Figure 3) and the configurations of two methoxyl groups at C-15 and C-16 were determined as a β-form. Therefore, the structure of 1 got the name "thujuoric acid A" and was defined as (15β,16β 7 The chemical shifts of H-12a and H12b of 2 (δ 2.28 and 2.00) in 1 H NMR spectrum were quite similar to those of 1 (δ 2.25 and 2.02), not to those of 3 (δ 2.35, 1.88), 6 indicating the relative configuration at C-16 of 2 was identical with the β form of 1. The NOESY correlations of 2 corroborated stereochemical structures ( Figure 3).…”

Bioactive Sesquiterpenes from the Essential Oil of Thuja orientalis

“…1). Herein we report the isolation and structural elucidation of isolates (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) propane ring in the molecule [11]. The 13 C NMR spectrum (l " Table 1) in combination with DEPT showed four tertiary methyls, three methines, four methylenes including a characteristic signal for the cyclopropane ring at δ C 10.9 [11], four quaternary carbons, and one methoxy carbon signals.…”

“…But, the chemical constituents of the essential oils have not been the main subject of most researches except for several GC/MS studies [5][6][7][8][9], in which α-pinene, Δ-3-carene, and α-cedrol were reported as the main components without any NMR data analyses. Our group has conducted a phytochemical investigation on the MeOH extract of the leaves of T. orientalis and reported the isolation of 13 diterpenoids including three new diterpenes that were cytotoxic [10]. In our continuing search for structurally interesting and bioactive constituents from T. orientalis, we investigated the chemical constituents of its essential oils.…”

“…The cytotoxic activities of the isolates (1-11) were evaluated by determining their inhibitory effects on human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) using the SRB bioassay [18]. The essential oils of this plant have been used to treat cancer [4], and we have recently identified the cytotoxic diterpenoids from this plant [10]. The results (l " , and 10; B: 2 and 4; C: 7, 9, and 11) with the same skeletal structure, the presence of a Δ 4,5 -double bond in the skeleton of this sesquiterpene may be critical to increase cytotoxic activity against the tested cell lines as compounds 4-6 and 9 with the Δ 4,5 -double bond in each group (A, B, and C) had a higher cytotoxicity, compared to the other compounds, though more related sesquiterpenes need to be tested to confirm this hypothesis.…”