Inhibitory effect of kaurane type diterpenoids fromAcanthopanax koreanum on TNF-α secretion from trypsin-stimulated HMC-1 cells

Abstract

Five known kaurane type diterpenoids, 16alphaH,17-isovaleryloxy-ent-kauran-19-oic acid (1), 16alpha-hydroxy-17-isovaleryloxy-ent-kauran-19-oic acid (2), paniculoside-IV (3), 16alpha-hydroxy-ent-kauran-19-oic acid (4), and ent-kaur-16-en-19-oic acid (5) were isolated from the root of Acanthopanax koreanum by repeated column chromatography and reversed phase preparative HPLC. The structures of these compounds were established from physicochemical and spectral data. Among the isolated compounds 16alphaH,17-isovaleryloxy-ent-kauran-19-oic acid (1) showed potent inhibitory activity (IC50 value, 16.2 uM) on TNF-alpha secretion from HMC-1, a trypsin-stimulated human leukemic mast cell line.

Absolute Configuration of a Diterpene with an Acyclic 1,2-Diol Moiety and Cytotoxicity of Its Analogues from the Aerial Parts of Aralia cordata

“…1 Previous phytochemical investigations on this plant have reported the isolation of several kinds of diterpenes having pimarane and kaurane skeletons. 2 In our current phytochemical investigation on the aerial parts of this plant has led to the isolation of a new ent-pimarane diterpene, ent-15S, 16-dihyroxypimar-8(14)-en-19-oic acid (1), together with three known diterpenes, ent-pimar-8 (14), 15-dien-19-oic acid (2) 3 , ent-16α-hydroxykauran-19-oic acid (3) 4 and ent-kaur-16-en-19-oic acid (4) 5 ( Figure 1). Although the structure of compound 1 was reported previously, 6 there has been no report of the isolation from natural sources.…”

“…Moreover, there has been no report on the determination of the absolute configuration of the 1,2-dihydroxyethyl moiety in 1. Therefore, in order to deduce the absolute configuration of this moiety, a CD method employing dimolybdenum tetraacetate [Mo 2 (AcO) 4 ] developed by Snatzke and Frelek 7 was applied to 1. The present paper reports the isolation and structure elucidation of isolated compounds (1-4) from the aerial parts of A. cordata and their cytotoxicity, as well as the determination of the absolute configuration of an acyclic 1,2-diol moiety in 1 using Snatzke's method.…”

“…Furthermore, the UVvis spectral region of acyclic 1,2-diols below about 190 nm prevents the use of chiroptical methods 13 for the direct analysis of their absolute configuration, unless a chemical derivatization is carried out on the chiral substrate by addition of a suitable chromophoric group. A possible way to solve this problem is application of a CD (circular dichroism) method employing dimolybdenum tetraacetate [Mo 2 (AcO) 4 ] as an auxiliary chromophore, which is one of the most useful method for rapid and effective determination of the absolute configuration of acyclic 1,2-diols. 7 In this method, the chiral substrate acts as a ligand of the metal center through ligation to the Mo 2+ core.…”

“…In order to deduce the absolute configuration of an acyclic 1,2-diol moiety in 1, a CD method employing dimolybdenum tetraacetate [Mo 2 (AcO) 4 ] developed by Snatzke and Frelek 7 was applied to 1, and obtained its CD spectrum in the region of 550-250 nm. According to the rule proposed by Snatzke, the sign of the CD band around 305 nm, which has been assigned to a metal-to-ligand charge-transfer transition, 7a correlates with the absolute configuration of the acyclic 1,2-diol moiety in the ligating structure.…”

“…Dimolybdenum tetraacetate [Mo 2 (AcO) 4 ] was purchased from Fluka. DMSO, spectroscopy grade, was obtained from Fluka.…”