Antimitotic properties

Figure 13 outlines our retrosynthetic analysis of epothilone D (49). Since epoxidation of epothilone D to give epothilone B (3) is the last step in all total syntheses of the latter, this is considered to be trivial. Furthermore, epothilone D shows a lower non-specific toxicity relative to its antimitotic properties. 

Nishiguchi GA, Graham J, Bouraoui A, Jacobs RS, Little RD (2006) 7,11-epi-Thyrsiferol Completion of Its Synthesis, Evaluation of Its Antimitotic Properties, and the Further Development of an SAR Model. J Org Chem 71 5936... 

NATURAL BRIDGED BIARYLS WITH AXIAL CHIRALITY AND ANTIMITOTIC PROPERTIES... 

From the above literature studies, it seems clear that semi-synthesis has turned out to be the method of choice to generate a whole range of novel allocolchicinoid compounds from readily available colchicine precursors. Some of these synthetic allocolchicinoids have very potent antimitotic properties, and they have been used as tools to study tubulin-ligand interactions. The recent discovery of phosphate 35 as a prodrug with anti-... 

These extensive SAR studies have shown that the rigid biaryl/nine-membered lactam structure of rhazinilam adopting a boat-chair conformation is an essential feature for its antimitotic properties. Moreover, the absolute aR configuration of the biaryl axis is, as in the allocolchicine and stegane series, absolutely required for biological... 

Another group of alkaloids with antimitotic properties are the bisindole alkaloids, such as vinblastine and vincristine, which have been isolated from Catharanthus roseus (Apocynaceae). These alkaloids also bind to tubulin (312). Both alkaloids are very toxic, but are nevertheless important drugs for the treatment of some leukemias. 

Owing to its antimitotic properties, colchicine should not be given during pregnancy (SED-9,158) (10). 

More recently a study on sulphonamide drugs binding to the colchicines site of tubulin has been reported [38]. A series of diarylsulfonamides containing an indole scaffold was also found to have antimitotic properties, and to bind to the colchicine site of tubulin in a reversible manner. 

Rhizoxin D is a 16-membered macrolide isolated from the fungus Rhizopus chinensis Rh-2 and it showed remarkable antimitotic properties. Rhizoxin D was synthesized from four subunits and the final step involved the Stille coupling of the oxazole fragment with an iodolactone [17]. 

Natural Bridged Biaryls with Axial Chirality and Antimitotic Properties... 

An excellent volume on the pyrrolizidine alkaloids has recently been published. The chemistry of these alkaloids is briefly discussed, but considerable emphasis is placed on their pharmacology and pathogenicity. In another reference, Culvenor and his collaborators discuss the hepatotoxicity, antimitotic properties, and the metabolism of these alkaloids. The significance of the alkylating properties in relation to the antimitotic activity, and the role of pyrroles formed in vivo, are also discussed. 

Epothilone 85 possesses antimitotic properties similar to those of paclitaxel and could therefore have utility in the treatment of cancer. A key intermediate in the synthesis of this natural product is 86, a C 2-C2i subunit of 8S.34 One approach to this compound employed the CBS reduction of ketone 87 to generate 88, an alcohol related to 86. 

JtWimeth y f- 8, f /a metham> i taH cyclohepta[a naphthti-teM<9-dimcthanoU I Cl 69653 NSC-234714, CMHMC4 mol wt 338,49. C 70.97%, H 10.12%, O L8,9l%. Novel tetracyclic diterpene antibiotic with antiviral and antimitotic properties, isolated from Cephalosporium aphidicola Fetch, It is a specific inhibitor of DNA < -polymerase. Description and K-ray crystallographic dele ruin of structure K. M. 

The ustiloxins, isolated from the fungus Ustilaginoidea virens associated with rice plants, show antimitotic properties by inhibiting microtubule formation (7S0, 781). Structurally, they are characterized by the presence of two peptide bonds and one tmusual tertiary alkyl-aryl ether connection. The first total synthesis of ustiloxin D (1205) was achieved in 2002 (782) by Joullie et al., followed by a shorter synthesis by Wandless et al. (783, 784). Later on, its synthesis was conducted again (785) along with ustiloxin F (1206) (786) in a more convergent manner than previously by Joullie et al. (Scheme 15.2). 

Apart from that, azelaic acid has antiviral and antimitotic properties. Finally, it can also act as an antiprohferant and a cytotoxin via the blockage of mitochondrial respiration and DNA synthesis. 

P. Delatour and Y. Richard, Embryotoxic and antimitotic properties of a benzimidazole series, Therapie, 1976, 31, 505-515. 

Synthesis by Direct Cross-Coupling Reaction Trauner and co-workers and Bowie and Trauner reported on a concise total synthesis of racemic rhazinilam 122 and rhazinal 123, axially chiral phenylpyrroles having potent antimitotic properties, through an aromatic C—H activation (Scheme 23.24). " To construct the lactam ring of the title compounds, the authors proposed the use of a palladium-catalyzed direct intramolecular cross-coupling reaction. 

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