Kurilosides A1, A2, C1, D, E and F—Triterpene Glycosides from the Far Eastern Sea Cucumber Thyonidium (= Duasmodactyla) kurilensis (Levin): Structures with Unusual Non-Holostane Aglycones and Cytotoxicities

Abstract

Six new monosulfated triterpene tetra-, penta- and hexaosides, namely, the kurilosides A1 (1), A2 (2), C1 (3), D (4), E (5) and F (6), as well as the known earlier kuriloside A (7), having unusual non-holostane aglycones without lactone, have been isolated from the sea cucumber Thyonidium (= Duasmodactyla) kurilensis (Levin) (Cucumariidae, Dendrochirotida), collected in the Sea of Okhotsk near Onekotan Island from a depth of 100 m. Structures of the glycosides were established by 2D NMR spectroscopy and HR-ESI mass spectrometry. Kurilosides of the groups A and E contain carbohydrate moieties with a rare architecture (a pentasaccharide branched by C(4) Xyl1), differing from each other in the second monosaccharide residue (quinovose or glucose, correspondingly); kurilosides of the group C are characterized by a unique tetrasaccharide branched by a C(4) Xyl1 sugar chain; and kurilosides of the groups D and F are hexaosides differing from each other in the presence of an O-methyl group in the fourth (terminal) sugar unit. All these glycosides contain a sulfate group at C-6 of the glucose residue attached to C-4 Xyl1 and the non-holostane aglycones have a 9(11) double bond and lack γ-lactone. The cytotoxic activities of compounds 1–7 against mouse neuroblastoma Neuro 2a, normal epithelial JB-6 cells and erythrocytes were studied. Kuriloside A1 (1) was the most active compound in the series, demonstrating strong cytotoxicity against the erythrocytes and JB-6 cells and a moderate effect against Neuro 2a cells.

Triterpene Glycosides from the Far Eastern Sea Cucumber Thyonidium (=Duasmodactyla) kurilensis (Levin): The Structures, Cytotoxicities, and Biogenesis of Kurilosides A3, D1, G, H, I, I1, J, K, and K1

“…17αH-orientation, common for the sea cucumber glycosides, was deduced from the ROE-correlation H-17/H-32. The same aglycone was found earlier in kuriloside F [19].…”

“…The positions The molecular formula of kuriloside A 3 (1) was determined to be C 54 H 87 O 29 SNa from the [M Na − Na] − ion peak at m/z 1231.5063 (calc. 1231.5059) in the (−)HR-ESI-MS. Kuriloside A 3 (1) as well as the reported earlier kurilosides A, A 1 , and A 2 [19] belong to the same group of glycosides, so these compounds have the identical monosulfated pentasaccharide chains that were confirmed by the coincidence of their 1 H and 13 C NMR spectra corresponding to the carbohydrate chains (Table S1). The presence of five characteristic doublets at δ H = 4.64-5.18 (J = 7.1-7.6 Hz), and corresponding signals of anomeric carbons at δ C = 102.…”

“…The analysis of the 13 C NMR spectrum of the aglycone part of 4 demonstrated its identity to the aglycone of kurilosides A 1 and C 1 , isolated earlier [19]. Therefore, kuriloside H (4) contains a 22,23,24,25,26,27-hexa-nor-lanostane aglycone with 9(11)-double bond and acetoxy-groups at C-16 and C-20.…”

“…Thus, kuriloside J ( 7) is a branched disulfated pentaoside with the sulfate groups bonding to C-6 Glc4 and C-6 MeGlc5 in the upper semi-chain. The analysis of the 1 H and 13 C NMR spectra of the aglycone part of kuriloside J (7) (Table 7) revealed the presence of the hexa-nor-lanostane aglycone having a 9(11)-double bond, similar to the majority of the other glycosides of T. kurilensis [19] Hence, kuriloside J ( 7) is characterized by the new hexa-nor-lanostane aglycone with a 16β-acetoxy,(20S)-hydroxy-fragment. Table 7.…”

“…The analysis of the 13 All these data indicate that kuriloside I (5 (6) as well as kuriloside I (5) belong to one group because they have identical trisulfated pentasaccharide chains and, therefore, parts of the 1 H and 13 C NMR spectra corresponding to the carbohydrate chains are coincident (Table 4). 22,23,24,25,26,27-hexa-nor-lanostane aglycone of kuriloside I 1 ( 6) is identical to that of kurilosides H (4), A 1 and C 1 [19] (Table S4) and characterized by the presence of 16β,(20S)-diacetoxy-fragment. 6), five signals of anomeric protons at δ H 4.65-5.12 (d, J = 7.2-7.9 Hz) and corresponding five signals of anomeric carbons at δ C 102.0-104.7, deduced by the HSQC spectrum, were observed, which indicated the presence of a pentasaccharide chain similar to compounds 5 and 6.…”