3355. Discodermolide

Nomenclature

CAS number: 127943-53-7
(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; YM-19020.
C33H55NO8; mol wt 593.79.
C 66.75%, H 9.34%, N 2.36%, O 21.56%.

Description and 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).

Chemical structure

Properties

Monoclinic white crystals, mp 115-116°. uv max (methanol): 210, 226, 235 nm (ε 35400, 19500, 12500). [α]D20 +14.0° (c = 0.6 in methanol); monohydrate: [α]D +20.1° (c = 1 in methanol).

Use

Reagent for mitotic studies.