Discodermolide

Title: Discodermolide
CAS Registry Number: 127943-53-7
CAS Name: (3R,4S,5R,6S)-6-[(2S,3Z,5S,6S,7S,8Z,11S,12R,13S,14S,15S,16Z)-14-[(Aminocarbonyl)oxy]-2,6,12-trihydroxy-5,7,9,11,13,15-hexamethyl-3,8,16,18-nonadecatetraenyl]tetrahydro-4-hydroxy-3,5-dimethyl-2H-pyran-2-one
Manufacturers' Codes: YM-19020
Molecular Formula: C33H55NO8
Molecular Weight: 593.79
Percent Composition: C 66.75%, H 9.34%, N 2.36%, O 21.56%
Literature References: Polyhydroxylated lactone isolated from the marine sponge, Discodermia dissoluta. Naturally occurring (+)-form stabilizes microtubles and inhibits cell proliferation with the same mechanism as paclitaxel, q.v. Isoln and structure determn: S. P. Gunasekera et al., J. Org. Chem. 55, 4912 (1990); correction: ibid. 56, 1346 (1991). Total synthesis: D. T. Hung et al., J. Am. Chem. Soc. 118, 11054 (1996). Review of total syntheses: I. Paterson, G. J. Florence, Eur. J. Org. Chem. 2003, 2193-2208. Series of articles on industrial-scale synthesis: S. J. Mickel et al., Org. Process Res. Dev. 8, 92-130 (2004). NMR soln structure determn: A. B. Smith, III et al., Org. Lett. 3, 695 (2001). Mechanism of action: D. T. Hung et al., Chem. Biol. 3, 287 (1996); E. ter Haar et al., Biochemistry 35, 243 (1996). Synergistic activity with paclitaxel in cancer cells: S. Honore et al., Cancer Res. 64, 4957 (2004).
Properties: Monoclinic white crystals, mp 115-116°. uv max (methanol): 210, 226, 235 nm (e 35400, 19500, 12500). [a]D20 +14.0° (c = 0.6 in methanol); monohydrate: [a]D +20.1° (c = 1 in methanol).
Melting point: mp 115-116°
Optical Rotation: [a]D20 +14.0° (c = 0.6 in methanol); [a]D +20.1° (c = 1 in methanol)
Absorption maximum: uv max (methanol): 210, 226, 235 nm (e 35400, 19500, 12500)
Use: Reagent for mitotic studies.
Disilane Disodium Dihydrogen Hypophosphate Disodium Phenyl Phosphate Disofenin Disophenol

Discodermolide
(+)-Discodermolide
Identifiers
CAS number 127943-53-7 N
PubChem 643668
ChemSpider 558787 YesY
UNII DHG59994DN YesY
KEGG C16746 YesY
ChEMBL CHEMBL364447 YesY
Jmol-3D images Image 1
Image 2
Properties
Molecular formula C33H55NO8
Molar mass 593.79 g/mol
Melting point 112–113 °C
 N (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

(+)-Discodermolide is a polyketide natural product found to stabilize microtubule. (+)-discodermolide was isolated by Gunasekera and his co-workers at the Harbor Branch Oceanographic Institute from the deep-sea marine sponge Discodermia dissoluta in 1990.[1] (+)-Discodermolide was found to be a potent inhibitor of tumor cell growth in several MDR cancer cell lines. (+)-discodermolide also shows some unique characters, including a linear backbone structure, immunosuppressive properties both in vitro and in vivo,[2][3] potent induction of an accelerated senescence phenotype,[4] and synergistic antiproliferative activity in combination with paclitaxel.[5] Discodermolide was recognized as one of the most potent natural promoters of tubulin assembly. A large number of efforts toward the total synthesis of (+)-discodermolide were directed by its interesting biological activities and extreme scarcity of natural sources (0.002% w/w from frozen marine sponge). The compound supply necessary for complete clinical trials cannot be met by harvesting, isolation, and purification. As of 2005, attempts at synthesis or semi-synthesis by fermentation have proven unsuccessful. As a result, all discodermolide used in preclinical studies and clinical trials has come from large-scale total synthesis.[6]