Epoxide moiety

The anti anginal agent diltiazem (104) is synthesized starting with opening of the epoxide moiety of with the anion of 2-nitrothiophenol to give 100. This is resolved with cinchoni-... 

For the construction of the I ring, the vinylic group introduced to activate the y-hydroxy epoxide moiety of 28 towards cyclization is an acrylic ester residue, which concomitantly allows cyclization on the allylic position, with formation of the tricyclic compound 29 containing the IJK fragment of the natural product, and fur-... 

In a versatile stereocontrolled total synthesis of (+)-vinblastine, Fukuyama used a base-promoted macrocyclization of the N-nosylate and the terminal epoxide moiety present in 88 as one of the key steps, giving the 11-membered-ring product 89 in 82% yield (Scheme 8.23) [42],... 

The formation of the epoxide moiety found in a number of compounds from the manumycin group of antibiotics (Scheme 10.22) might proceed through a similar... 

The methyl group is delivered syn to the epoxide via an intermediate chelate between the organometallic reagent and the epoxide oxygen. Consistent with this hypothesis is the observation that the civ selectivity is increased as the solvent polarity is decreased and that addition of trimethylaluminum, which can strongly coordinate to the epoxide, gives nearly exclusively the trans-product. In the latter reaction, it was assumed that the addition of methylcopper occurs anti to the chelated epoxide moiety, possibly via an SN2 mechanism20. 

The stereochemical outcome of the reaction of 1-43, formed from 1-40 by desily-lation, can be explained by assuming a pseudoequatorial orientation of the epoxide moiety in a pseudo-chair-chairlike transition state 1-44 which, after being attacked by the phenolic oxygen, furnishes the correct trans-fused stereoisomer 1-41 (Scheme 1.12). The conformation 1-45, which would lead to 1-46 seems to be disfavored. 

The process is assumed to take place by a chemoselective attack of the dianion 2-223 at the bromomethyl group of 2-221 and subsequent nucleophilic attack of the resultant monoanion 2-224 onto the epoxide moiety to give 2-225. Use of the sodium-lithium-salt 2-223 of the dicarbonyl compound 2-220, the reaction temperature as well as the Lewis acid LiC104, are crucial. The reaction seems to be quite general, since various 1,3-dicarbonyl compounds can be converted into the corresponding furans. 

However, in order to avoid the epoxide moiety in 4-67, which might serve as a locus of nondiscrimimating cell toxicity, these authors focused their activity on the cyclopropane-analogue 4-70 by heating a mixture of 4-68 and 4-69, which led to 4-70 with extrusion of isobutene in 75% yield (Scheme 4.15). 

A similar domino process involving the opening of two epoxide moieties after an enzymatic ester hydrolysis has been described by Robinson and coworkers [16]. Treatment of 8-32 with PLE in an aqueous buffer solution at pH 7.5-8 led to 8-34 in 70% yield after formation of 8-33 (Scheme 8.8). 

A silastannation product bearing an epoxide moiety undergoes titanium(m)-mediated cyclization with the vinyl-stannane moiety (Equation (109)).268... 

Grafting can also provide the monolithic polymers with rather unexpected properties. For example, the two-step grafting procedure summarized in Fig. 7, which involves the vinylization of the pore surface by reaction of the epoxide moiety with allyl amine, and a subsequent in situ radical polymerization of N-isopropylacrylamide (NIPAAm) initiated by azobisisobutyronitrile within these pores leads to a composite that changes its properties in response to external temperature [76]. 

Reactions at the Epoxide Unit Reactions Adjacent to the Epoxide Moiety... 

Reactions have been carried out adjacent to the epoxide moiety in order to examine the effects, if any, that the epoxide has on subsequent reactions with respect to the regio- and stereochemical outcome. Dihydroxylation using osmium tetraoxide and Sharpless asymmetric dihydroxylation reactions have been extensively studied using substrates 29 and 31. Initial studies centred on the standard dihydroxylation conditions using AT-methylmorpholine-AT-oxide and catalytic osmium tetraoxide. The diastereomeric ratios were at best 3 2 for 29 and 2 1 for 31, indicating that the epoxide unit had very little influence on the stereochemical outcome of the reaction. This observation was not unexpected, since the epoxide moiety poses minimal steric demands (Scheme 21). 

Chemical/Physical. At 230 °C, endrin isomerizes to an aldehyde and a ketone. When heated to decomposition, hydrogen chloride and phosgene may be released (NIOSH, 1997) but residues containing an aldehyde (15-20%), a ketone (55-60%), a caged alcohol (5%), and other volatile products (15-20%) were reported (Phillips et al., 1962). In water, endrin undergoes nucleophilic attack at the epoxide moiety forming endrin diol (Kollig, 1993). 

Chemical/Physical. Heptachlor epoxide will hydrolyze via nucleophilic attack at the epoxide moiety forming heptachlor diol which may undergo hydrolysis forming heptachlor triol and hydrogen chloride (Kollig, 1993). 

In 1993, Yoshida et al. pubhshed trapoxin (TPX, Fig. 3), a fimgal product, which, in contrast to TSA, is an irreversible inhibitor of mammalian histone deacetylase [38]. When the epoxide moiety is reduced to the corresponding primary alcohol, HDAC inhibiting activity is completely lost. This observation emphasizes the importance of the oxirane ring, which most likely binds irreversibly via ring opening at the activated 2-position to a nucleophihc active site residue. 

In 1993, Oki et al. isolated the novel carbazole antibiotics epocarbazolin A (258) and B (259) from the culture broth of Streptomyces anulatus T688-8 (230). They represent the first carbazole alkaloids with an epoxide moiety in a side chain, and are the epoxides corresponding to carbazomadurin A (256) and B (257). Epocarbazolin A (258) [oC + 75.0 (c 0.5, MeOH) and B (259) Mg -b 78.0 (c 0.5, MeOH) were obtained from Nature in optically active form. However, their absolute configuration is not known. These alkaloids showed potent 5-lipoxygenase inhibitory activity and weak antibacterial activity (230) (Scheme 2.63). 

More structurally complex epoxides can be ring-opened intramolecularly in a synthetically useful fashion. Thus, in their approach to methyl-substituted trmis-fused tetrahydropyran subunits found in marine natural products, Mori and co-workers <99TL8019> treated the polyfunctional arylsulfonyl epoxide 67 with Lewis acid to induce a (s-endo cyclization onto the epoxide moiety, with concomitant ejection of arylsulfinate, to provide the bicyclic ether 68. This system was found to be highly sensitive to the nature of the Lewis acid catalyst used. 

Glycidol possesses a reactive epoxide moiety. This is likely to be responsible for the genotoxic activity of the compound without a requirement for metabolic activation. 

In the event, iodolactonization of the carboxylate salt derived from the ester 458 afforded 459, and subsequent warming of the iodo lactone 459 with aqueous alkali generated an intermediate epoxy acid salt, which suffered sequential nucleophilic opening of the epoxide moiety followed by relactonization on treatment with methanol and boron trifluoride to deliver the methoxy lactone 460. Saponification of the lactone function in 460 followed by esterification of the resulting carboxylate salt with p-bromophenacylbromide in DMF and subsequent mesylation with methanesulfonyl chloride in pyridine provided 461. The diazoketone 462 was prepared from 461 by careful saponification of the ester moiety using powdered potassium hydroxide in THF followed by reaction with thionyl chloride and then excess diazomethane. Completion of the D ring by cyclization of 462 to the keto lactam 463 occurred spontaneously on treatment of 462 with dry hydrogen chloride. 

The cytotoxicity of taxoids 40-i and 40-S bearing the oxanorstatine residue were evaluated in our standard five human cancer cell line assay.71 As Table 7 shows, these two stereoisomers were found to possess considerably different cytotoxicity, which is rather unexpected. Taxoid 40-R showed a 3- to 10-fold increase in activity as compared to paclitaxel, while the other isomer, taxoid 40-S, exhibited a 2- to 4-fold decrease in activity, i.e. one to two orders of magnitude difference in activity is observed just by changing the stereochemistry of the epoxide moiety at C-3. This... 

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