Microtubule stabilizing agents discodermolide

Balachandran, R., Terhaar, E., Welsh, M.J., Grant, S.G., and Day, B.W (1998) The potent microtubule-stabilizing agent (+)-discodermolide induces apoptosis in human breast carcinoma cells preliminary comparisons to paclitaxel. Anti-Cancer Drugs, 9, 67-76. 

Gunasekera, S.P., Longley, R.E., and Isbmcker, R.A. (2001) Acetylated analogues of the microtubule-stabilizing agent discodermolide preparation and biological activity. J. Nat. Prod., 64,171-174. 

Klein, L.E., Freeze, B.S., Smith, A.B. 111, and Horowitz, S.B. (2005) The microtubule stabilizing agent discodermolide is a potent inducer of accelerated senescence. Cell Cycle, 4, 501-507. 

Canales A, Matesanz R, Gardner NM, Andreu JM, Paterson I, Diaz JF, Jimenez-Barbero J (2008) The bound conformation of microtubule-stabilizing agents (II) NMR insights on the bioactive 3D structure of discodermolide and dictyostatin. Chemistry (DOI 10.1002/chem.200800039)... 

Chart 9 Schematic representation of the principal microtubule stabilizing agents (MSAA) paclitaxel (10) and docetaxel (11), epothilones A-D (12-15), discodermolide (16), eleutherobin (17) and sarcodictyin (18), laulimalide (19) and peloruside A (20)... 

A small, but structurally diverse collection of naturally occurring non-taxane microtubule stabilizing agents (MTS) has been discovered over the last decade. These include the epothilones (EPO), eleutherobin, laulimalide, dicytostatin (Figure 2) and (+)-discodermolide. 

Paterson, 1., Florence, G. j.,The development of a practical total synthesis of discodermolide, a promising microtubule-stabilizing anticancer agent, Eur. J. Org. Chem. 2003, 2193-2208. 

The natural product eleutherobin (1) was isolated in 1994 by Fenical et al. from a marine soft coral from an Eleutherobia species and its structure was elucidated shortly afterwards (Figure 1) [1]. Eleutherobin is a diterpene glycoside that possesses remarkable cytotoxicity against a wide variety of cancer cells, which is likely to be based on binding to tubulin and stabilization of microtubules [2, 3]. Mitosis is interrupted and the cell division cycle is terminated. The mechanism of action of eleutherobin is comparable to that of highly potent cytostatic agents such as paclitaxel (Taxol), nonataxel, epothilones, and discodermolide. 

S. P., Rosenkranz, H. S., Day, B. W., Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol. Biochemistry 1996,... 

Discodermolide (3) is a polypropionate-based unique compound isolated from the Caribbean deep-sea sponge Discodermia dissoluta. It is immunosuppressive as well as highly cytotoxic. More significantly, it stabilizes microtubules more potently than taxol. " Attempts at large-scale synthesis were carried out for clinical trials as an anticancer agent but the clinical trials were discontinued in 2005 due to its toxicity. ... 

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