Epoxide moiety, modifications

A large part of the early SAR work on epothilones has focused on modifications of the epoxide moiety at positions 12/13 of the macrolactone ring. These studies have demonstrateded that the presence of the epoxide ring is not an indispensible prerequisite for efficient microtubule stabilization and potent antiproliferative activity. Thus, Epo C (10) and D (11) (Figure 1-1) are virtually equipotent inducers of tubulin polymerization as Epo A and B, respectively. They are also potent inhibitors... 

Modification of the cyclohexenyl moiety has been carried out by use of the cyclohexadiene epoxides 243 and 244, which were coupled with methyl 4-amino-4-deoxy- and -4,6-dideoxy-0 -D-glucopyranoside (385a and 385b) to give the isomers (395 and 396). 

Another modification of a cyclopentene moiety was achieved by the cycloaddition reaction of the 1,3-dithiolane derivative 483 with singlet oxygen O2 to form the endoperoxide 484, which upon treatment with either triethyl-amine, triphenylphosphine, or bromine gave the corresponding hydroxy ketone 485, a mixture of the epoxide 486 and the enonc 487, or a mixture of isomeric adducts 488 and 489, respectively (Scheme 69) <1995JOC1333>. 

All the precursors are easily prepared by epoxidation and alkylation of the Diels-Alder adduct of p-benzoquinone and dimethylfulvene, and subsequent pyrolyses of the precursors in a sealed tube under rather mild conditions to yield these epoxy compounds [20-22]. Although there are other methods to prepare such quinone epoxides and a-epoxycyclohexenones, the advantages of the retro Diels-Alder method are as follows 1. epoxidation of quinone adducts proceeds regioselectively to give an epoxide, in which the more substituted double bond in the starting quinone is epoxidized, 2. the adducts are usually stable, and are able to afford appreciably modified quinone moieties, 3. stereoselectivities are expected in the modification of the ewiAj-adducts. 

The most important inference is that Chemisorption is a direct response to carboxyl group concentration indicated by the XPS photopeak component at 288.7 eV. It seems likely that weak add functionality is of minor import to applications for surface treatments, while interfacial phenomena such as practical adhesion may be sensitive to small concentrations of very high site energies. Interphase modification in epoxy resins, for example, can occur by direct reaction of epoxide groups with surface carboxyls (17), or by accelerated cure chemistry near the surface (39). Carboxyl groups on carbon surfaces may interact with basic moieties in polymers such as polycarbonate or poly(ethylene)oxide (40=42), or promote interfacial crystallinity that improves impact strength and other aspects of composite performance (43, M)-... 

Monodispersed (polydispersity index = 1,04) polystyrene and polyisoprene with a molecular weight in the range of 2 x 10 were used as the carrier polymers by Bates and Baker [18,51]. The isoprene polymer was synthesized anionically at -78°C using toluene as the solvent. It was composed of approximately 80% cis 1,4, 15% trans-, A and 15% 3,4-disubstitutedrepeating units. A few percent (3%) of butadiene were randomly copolymerized with styrene anionically at 25°C in order to provide unsaturated moieties for the next modification step. Electrophilic sites were then introduced into the respective carrier polymers by either oxidation or epoxidation. It was expected that the sites consist mainly of aldehydes, ketones, and/or epoxides. ffj-Chloroperbenzoic acid (m-CPBA) was found to be effective in epoxidation of the unsaturated moieties in... 

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