Epidioxide

Oxidation of dihydrocoptisine (124), derived from protopine, with m-chloroperbenzoic acid in dichloromethane afforded coptisinephenolbetaine (125) as the hydrochloride in 78% yield (Scheme 26) (82). This oxidation method was applied to dihydroberberine (90) to produce berberinephenolbetaine (121) (53). Additionally, photooxygenation of 90 in methanol containing Rose Bengal gave 121 in 80% yield, further photooxygenation of which led to the epidioxide 122, a 1,3-dipolar cycloaddition product with oxygen (84,85). 

Scheme 68. Synthesis of phthalideisoquinolines from prechilenine (139) and the epidioxide. Reagents a, 25% H2SC>4 b, KOH then cone H2S04 c, py-HCl, py d, Me2S04 e, CH3I. 

Acidic treatment of prechilenine (139) (Section III,C) afforded the imino keto acid 377 via the imminium salt 140 (Scheme 68). Neutralization and work-up furnished the known y-lactol 371 in 90% overall yield from 139 (96, 181). Kondo et al. (183) obtained 139 from the epidioxide 122 by treatment with pyridine hydrochloride in pyridine along with 377 and norhydrastine. The acid 377 was converted to the known imino ester 373 through N,0-dimethylation. 

An alternative synthesis of 22,23-dihydroergosteryl acetate involved hydrogenation of the epidioxide (249) to the saturated 5a,7a-dihydroxy-derivative (250). This was followed by an improved carefully controlled dehydration with... 

Two syntheses have been reported for 14j8-hydroxyandrostan-17-ones which are useful intermediates in cardenolide synthesis. Photo-oxygenation of 5a-androsta-14,16-diene gave the epidioxide (296) which was transformed with base into... 

D Ambrosio, M. Guerriero, A. Deharo, E. Debitus, C. Munoz, V. Pietra, F. (1998) New types of potentially antimalarial agents norditerpene and norsesterterpene epidioxides from the marine sponge Diacarnus levii. Helv. Chim. Acta, 81, 1285-92. 

The peaks in the chromatograms most likely represent not only primary but also secondary oxidation products of TAGs. According to Neff and co-workers (140), the minor peaks eluting before the main peaks of standard compounds illustrate secondary oxidation products, such as hy-droperoxy epidioxides or bis- or tri.v-hydroperoxides. 

These cyclic peroxides are also known as photooxides, transannular peroxides, 1,4-epiperoxides, and epidioxides. 

Homoannular dienes e.g. i) readily add excited oxygen in a reaction which is the photochemical equivalent of the Diels-Alder diene-addition reaction fyjJ. The resulting epidioxides e.g. 2) are sufficiently stable for isolation/although they are fairly reactive [72]. 

Levopimaric acid forms an epidioxide (63) which thermally rearranges to a di oxide (65). On photolysis the epidioxide gives both the diepoxide and the 12-keto-epoxide (64). Treatment of the epidioxide with triphenylphosphine affords a monoepoxide which was shown to be the 8a(14a)-epoxide (66). On further epoxidation this gave the diepoxide, levopimaric acid dioxide. The photochemistry of ring c diterpenoid y-hydroxydienones has also been investi-gated. " Thus compound (67 R = H or Et) afforded firstly the spiro-diketone (68) and then the unsaturated y-lactone (69). 

The eosin-sensitized photo-oxygenation of 3jS-hydroxyandrosta-5,7-dien-17-one (181) provides a mixture of 5a,8-epidioxide (182a), 5,8-dien-7-one (182b), and both isomeric allylic alcohols (183a) and (183b). Palladium-catalysed treatment of (182a) gave the triol (184), which was then converted into the triene-dione (185) °. 

Ozone adds directly to double bonds in fatty acids to form ozonides (183-185). These decompose to lipid alkoxyl and peroxyl radicals that abstract hydrogens to initiate radical chains (186). In the process, internal rearrangements within the original lipid molecule(s) yield hydroxy epoxides and hydroxy epidioxides with 1,3- and 1,4-cyclic hydroperoxides ... 

Hydrogen abstraction also increases at elevated temperature as thermal energy decreases bond dissociation energy. Typical H abstraction rates for ROO at room temperature are < 1 M s, but this increases to 10 -10" L M s at 65°C (223). For example, in linolenic acid autoxidized neat at room temperature to PV 1113, products were not quantified, but estimates from intensities of HPLC peaks gave about 40% LnOOH, 12% dihydroperoxides, 12% hydroperoxy epidioxides, and 4% epoxides (228). At 40°C, H abstraction occurred more as a secondary process. Hydroperoxides per se were still the main products, but fewer were present as mono- and dihydroperoxides (36% total) and more had formed after cyclization or addition (31%). Data are not available to distinguish whether this... 

Propagation via addition of LOO to double bonds forms both monomer products (epoxides and epidioxides) and dimers or polymers the propagating species are peroxyl radicals formed at new positions and alkoxyl radicals released by p-elimination. In early stages of oxidation, LOO adds to double bonds to form an initial dimer complex (Reaction 48), which then reacts further to generate new radicals. The ultimate product depends on the nature of the target double bond. 

LOO additions increase with heat (289), extent of oxidation (290), and solvent polarity (266). Dimer levels of methyl linolenate autoxidized neat at room temperature varied from 0.1% to 10.1%, proportional to peroxide values (290). MLn autoxidized at 40°C to PV 1062 gave 6.8% dimers 80% of these were from LOO and 20% were from epidioxide-OO additions. The dimer linkages were mostly C—O—O—C at lower temperatures, but shifted to C—C and C—O—C as the temperature increased (276). At PV = 4002, LOO additions increased to 55% of the products. Epidioxide peroxyl radicals, in particular, showed a very strong tendency to add to double bonds, with greater than 90% dimerization at 40°C. 

Review of all the scission reactions responsible for the hundreds of volatile products in lipid oxidation is beyond the scope of this chapter. The reader is referred to the available reviews (3, 314, 340, 341, 347) for further details. The scission pattern of hydroperoxide epidioxides from linoleic acid is included here to show how the decompositions can become quite complex (Figure 14), and lists of typical products resulting from scission reactions of oleic, linoleic, and linolenic acids are presented in Table 12. 

Figure 14. Secondary scissions of intermediate products make important contributions to the totai mix of compounds generated during iipid oxidation, shown here for iinoieic acid and esters. Top Oxidation and subsequent scission of radicais reieased in scissions ofinitiai aikoxyi radicais augment some of the originai scission aidehydes, aithough by different routes, and produce some different compounds as weii, inciuding the pentyi furan responsibie for reversion fiavor in oiis. Simiiariy, decomposition of epidioxides formed during photosensitized oxidation of iinoieate increase yieids of major aidehydes and aiso produce ionger chain aidehydes. Adapted from (273, 314).

Hydrogenolysis of dialkylperoxides or epidioxides (cyclic peroxides) also takes place over these same catalysts under mild conditions. If tertiary alcohols are the products, running the reaction in acid media can lead to dehydration. Deactivated catalysts are also needed if the product contains an allyl alcohol that could be cleaved by the more active catalysts (Eqn. 20.72). 6.I87... 

A selective reducing agent for double bonds (potassium azodicarboxylate-acetic acid) allowed the preparation of the epidioxide (268) from the A -compound/ A synthesis was reported for the 18,20-lactone (269) through the hypoiodite reaction of (205)-20-hydroxy-5a-cholestan-3/3-yl acetate/ A second synthesis of the 18,20-lactone (269) from the known lactone (270) involved the stereoselective reaction of the acetoxy-ketone (271) with iso-hexylmagnesium bromide to give the (205)-20-hydroxy-compound (272)/ These syntheses served as models for the synthesis of seychellogenin (273) and the 7,8,9,11-tetrahydro-derivative/ ... 

Epidioxides (sometimes called endoperoxides) can be prepared from acenes, from suitable steroids, and from dienes of low molecular weight ([Pg.274]

The leaf tissue of mature plants of some eucalyptus species, eg E. grandis, produce amounts (up to 7.5 mg/g dry wt) of three plant growth regulators, the G-inhibitors (55-57), which are characterised by the presence of an epidioxy functionality. Since these compounds lacked optical activity, the possibility that they were artefacts was considered. In fact, the (3-triketone (58) (Scheme 2) rapidly formed the epidioxide (57) on exposure to air. However, isolation of the inhibitors in the presence of 1802 did not result in incorporation of isotopic oxygen. It has been suggested that (55-57) arise from the corresponding Mannich bases which are con-... 

Reduction of epidioxides. Schenck and Dunlap used thiourea for reduction of epidioxides, obtained by 1,4-addition of singlet oxygen to conjugated dienes at low temperatures, to the corresponding diols. Kaneko et al. report that the diols can be obtained in one step by irradiation of the diene with singlet oxygen in the presence of thiourea. Under these conditions irradiation can be conducted conveniently at room temperature. This procedure was used to prepare cw-2-cyclopentene-l,4-diol and cw-2-cyclohexene-l,4-diol. 

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