Cytotoxic glycoside

Zampella A, D Auria MV, Minale L, Debitus C (1997) Callipeltosides B and C, Two Novel Cytotoxic Glycoside Macrolides from a Marine Lithistida Sponge Callipelta sp. Tetrahedron 53 3243... 

Investigation on the dichlorometane extract obtained from several collections of the New Caledonia sponge Callipelta sp., led to the isolation of new cytotoxic glycosides, callipeltosides A-C (122-124) [133,134], Structural assignment of callipeltosides was accomplished through extensive 2D NMR spectroscopy. The complete relative stereochemistry was proposed on the basis of the analysis of ROESY and NOE difference experiments. Callipeltoside A (122) is the first member of an unprecedented class of marine natural products with unusual structural features such as the previously unknown 4-amino-4,6-dideoxy-2-0,3-C-dimethyl-a-talopyranosyl-3,4-urethane (callipeltose), linked... 

Further fractionation of the active ethanol extract of Desfontainia spinosa based on cytotoxicity has led to the discovery of two novel, cytotoxic glycosides of the parent, 11-deoxocucurbitacin I, named spinoside A (8) and spinoside B (9). The structures of 8 and 9 were established on the basis of extensive analysis of their high field NMR, NMR, high resolution mass spectra (FAB, FD, Cl, El) and chemical interconversions (ref. 57). The novel arabinopyranoside derivatives of 6 were less cytotoxic than the parent compound in the 9PS system. Cucurbitacins although highly cytotoxic have never demonstrated significant anticancer effects in vivo. 

Figure 6. Cytotoxic Glycosides from Desfontainia spinosa...

Ikeda, T, Fujiwara, S., Araki, K., Kinjo, J., Nohara, T., Miyosh, T Cytotoxic glycosides from Albizia julibrissin. J. Nat. Prod. 60, 102-107 (1997)... 

Zampella, A., D Auria, M.V., Minale, L, and Debitus, C. (1997) CaEipdtosides B and C, two novel cytotoxic glycosides tnacrolides from a marine Lilhistida sponge CaBipdta sp. Tetrahedron, 53,3243-3248. 

Maia, L.E., Epifanio, R.A., and Fenical, W. (2000) New cytotoxic glycosides from the octocoral Carijoa Telesto) riisei. J. Nat. Prod., 63, 1427-1430. 

Vongvanich N, Kittakoop P, Kramyu J, Tanticharoen M, Thebtaranonth Y. Phyllan-thusols A and B, cytotoxic norbisabolane glycosides from Phyllanthus acidus Skeels. J Org Chem 2000 65 5420-5423. 

A more complex structure is that of leinamycin 45 (Scheme 15), a material with potent cytotoxic and antitumor properties, isolated from a Streptomyces sp. A 1,2 dithiolane-3-one ring is spiro fused to a complex macrolactam96 (and references therein). Leinamycin has the remarkable ability to cleave DNA. In brief, leinamycin reacts with a thiol and, after a profound rearrangement, forms an episulfonium ion. This ion alkylates the N7 position of guanosine residues in double stranded DNA an unstable adduct is depurinated by hydrolysis of the glycosidic bond between the alkylated base and a deoxyribose residue. Some structurally less complex l,2-dithiolane-3-one 1-oxides have a similar DNA cleaving ability.97... 

The synthesis of the disaccharide subunit 85 of tricolorin A, a cytotoxic resin glycoside isolated from lpomoea tricolor, provides a unique opportunity to compare the efficiency of an RCM-based macro cyclization reaction with that of a more conventional macrolactonization strategy. Furthermore, this specific target molecule challenges the compatibility of the catalysts with various functional groups. 

The route for the cytotoxic ipomoeassin resin glycosides relied on the use of compound 256 as a new cinnamic acid surrogate with its trisubstituted double bond and meets the requirement of being hydrogenation resistant in the presence... 

The cytotoxic potential of several resin glycosides has been evaluated against mammalian cancer cultured cell lines. For tricolorin A (106), the most potent cytotoxic activity (ED q 2.2 pg/cm ) was observed with human breast cancer and... 

Leon I, Enriquez RG, Gnecco D, Villareal ML, Cortes DA, Reynolds WF, Yu M (2004) Isolation and Characterization of Five New Tetrasaccharide Glycosides from the Roots of Ipomoea stans and Their Cytotoxic Activity. J Nat Prod 67 1552... 

Mimaki, Y. et al., Flavonol glycosides and steroidal saponins from the leaves of Cestrum noctur-num and their cytotoxicity, J. Nat. Prod., 64, 17, 2001. 

Ismail, N. and Alam, M., A novel cytotoxic flavonoid glycoside from Physalis angulata, Fitoter-apia, 72, 676, 2001. 

Xu, Y., Kubo, L, and Ma, Y., A cytotoxic flavanone glycoside from Onychium japonicum structure of onychin, Phytochemistry, 33, 510, 1993. 

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