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.

Nine new mono-, di-, and trisulfated triterpene penta- and hexaosides, kurilosides A3 (1), D1 (2), G (3), H (4), I (5), I1 (6), J (7), K (8), and K1 (9) and two desulfated derivatives, DS-kuriloside L (10), having a trisaccharide branched chain, and DS-kuriloside M (11), having hexa-nor-lanostane aglycone with a 7(8)-double bond, have been isolated from the Far-Eastern deep-water sea cucumber Thyonidium (=Duasmodactyla) kurilensis (Levin) and their structures were elucidated based on 2D NMR spectroscopy and HR-ESI mass-spectrometry. Five earlier unknown carbohydrate chains and two aglycones (having a 16β,(20S)-dihydroxy-fragment and a 16β-acetoxy,(20S)-hydroxy fragment) were found in these glycosides. All the glycosides 1-9 have a sulfate group at C-6 Glc, attached to C-4 Xyl1, while the positions of the other sulfate groups vary in different groups of kurilosides. The analysis of the structural features of the aglycones and the carbohydrate chains of all the glycosides of T. kurilensis showed their biogenetic relationships. Cytotoxic activities of the compounds 1-9 against mouse neuroblastoma Neuro 2a, normal epithelial JB-6 cells, and erythrocytes were studied. The highest cytotoxicity in the series was demonstrated by trisulfated hexaoside kuriloside H (4), having acetoxy-groups at C(16) and C(20), the latter one obviously compensated the absence of a side chain, essential for the membranolytic action of the glycosides. Kuriloside I1 (6), differing from 4 in the lacking of a terminal glucose residue in the bottom semi-chain, was slightly less active. The compounds 1-3, 5, and 8 did not demonstrate cytotoxic activity due to the presence of hydroxyl groups in their aglycones.