Natural epoxidized

There are two sources of epoxidized triglycerides, the first is the isolation of naturally epoxidized oUs, and the other is the preparation of epoxidized triglycerides via oxidation of the more readily available unsaturated seed oils. 

In Nature, epoxide ring-opening is catalyzed by enzymes by employing the (double) hydrogen-bonding motif (Scheme 6.1) for epoxide activation toward... 

Asymmetric synthesis. Following the procedure of Cope et al. (2, 272), Chamberlain and McKervey1 prepared the optically active complex (3) of humulene (1) by treatment with (—)-/ranj-dichloro(ethylene)-a-methylbenzylamine platinum-(11), (2). Epoxidation of (3) with perlauric acid gives optically inactive humulene (1) and humulene 1,2-epoxide with ctD= —3.2°. Since the natural epoxide has an... 

Photooxygenation of a -dimethylstyrene. This reaction has been used in a synthesis of ( )-crotepoxide (6), a natural epoxide with activity against some... 

Another interesting oilseed crop tiiat has been researched in our laboratories for several years is Euphorbia lagascae (22) (Fig. 3). This oilseed crop contains vemolic acid (12,13 -epoxy-cis-9-octadecenoic acid), with a natural epoxide content of 65% (see Table 2). 

Other triglyceride oils that are being investigated as IPN monomers include vemonia oil and lesquerella oil. Vernonia oil, a naturally epoxidized oil. 

In Chapter 12 we will see other three-membered rings found in Nature. Epoxides are used as triggers in the construction of the biologically active molecules called steroids, and, amazingly enough, one of the most prominent molecules in interstellar space is not only a cyclopropene, but a carbene as well. This molecule is known as cyclopropenylidene ... 

Some plant oils have, naturally, high functionality and can be used without modifications to produce different polymeric materials. Such is the case for V. galemensis, a natural epoxidized planL which contains 60-65% vemo-Uc acid. Castor oil is a hydroxyl-containing oil with -90% of ricinoleic cid. 

Hydroperoxide-dependent peroxygenase (epoxygenase). This enzyme, detected in soybeans [7] and broad beans [8], controls the fatty acid hydroperoxide-dependent epoxidation of unsaturated fatty acids. Hydroperoxide molecule plays a role of oxygen donor for epoxidation. This pathway was proposed as the source of natural epoxides of linoleate, vemolic and coronaric acids, occurring in different amounts in many seed oils. 

Synthesis The Diels-Alder reaction is simply the dimerisation of isoprene to giye the naturally occurring terpene A. Now we haye to cleaye one double bond and leaye the other alone. It turns out that epoxidation is selectiye in this case. 

The method has been applied in asymmetric and regioselective syntheses of several natural compounds. Two simple examples are the commercial syntheses of the gipsy moth hydrophobic sex attractant, disparlure (RE. Rossiter, 1981, 1985) and < mono-epoxidation of a diene in a leukotriene B4 synthesis (L.S. Mills, 1983). 

Functional group transformations of epoxides rank among the fundamental reactions of organic chemistry and epoxides are commonplace natural products The female gypsy moth for example attracts the male by emittmg an epoxide known as disparlure On detechng the presence of this pheromone the male follows the scent to its ongm and mates with the female... 

Many naturally occurring substances are epoxides You have seen two examples of such compounds already m disparlure the sex attractant of the gypsy moth (Section 6 18) and m the carcinogenic epoxydiol formed from benzo[a]pyrene (Section 118) In most cases epoxides are biosynthesized by the enzyme catalyzed transfer of one of the oxy gen atoms of an O2 molecule to an alkene Because only one of the atoms of O2 is trans ferred to the substrate the enzymes that catalyze such transfers are classified as monooxy genases A biological reducing agent usually the coenzyme NADH (Section 15 11) is required as well... 

Section 16 14 Epoxide functions are present m a great many natural products and epox ide ring opening is sometimes a key step m the biosynthesis of other sub stances... 

Epoxide-opening iatramolecular cycli2ations, in light of their importance in natural product chemistry, have received much attention (62). 

Typically, soHd stabilizers utilize natural saturated fatty acid ligands with chain lengths of Cg—C g. Ziac stearate [557-05-1/, ziac neodecanoate [27253-29-8] calcium stearate [1592-23-0] barium stearate [6865-35-6] and cadmium laurate [2605-44-9] are some examples. To complete the package, the soHd products also contain other soHd additives such as polyols, antioxidants, and lubricants. Liquid stabilizers can make use of metal soaps of oleic acid, tall oil acids, 2-ethyl-hexanoic acid, octylphenol, and nonylphenol. Barium bis(nonylphenate) [41157-58-8] ziac 2-ethyIhexanoate [136-53-8], cadmium 2-ethyIhexanoate [2420-98-6], and overbased barium tallate [68855-79-8] are normally used ia the Hquid formulations along with solubilizers such as plasticizers, phosphites, and/or epoxidized oils. The majority of the Hquid barium—cadmium formulations rely on barium nonylphenate as the source of that metal. There are even some mixed metal stabilizers suppHed as pastes. The U.S. FDA approved calcium—zinc stabilizers are good examples because they contain a mixture of calcium stearate and ziac stearate suspended ia epoxidized soya oil. Table 4 shows examples of typical mixed metal stabilizers. 

The optical activity of malic acid changes with dilution (8). The naturally occurring, levorotatory acid shows a most peculiar behavior in this respect a 34% solution at 20°C is optically inactive. Dilution results in increasing levo rotation, whereas more concentrated solutions show dextro rotation. The effects of dilution are explained by the postulation that an additional form, the epoxide (3), occurs in solution and that the direction of rotation of the normal (open-chain) and epoxide forms is reversed (8). Synthetic (racemic) R,.9-ma1ic acid can be resolved into the two enantiomers by crystallisation of its cinchonine salts. 

Pyrethroids from Chiysanthemic Acid. The unsaturated side chains of the aHethrolone alcohol moieties of the natural pyrethrins are readily epoxidized by microsomal oxidases and converted to diols, thus detoxifying the insecticides. Esterification of chrysanthemic acid (9), R = CH3, with substituted ben2yl alcohols produces usehil insecticides barthrin [70-43-9J, 2-chloro-3,4-methylenedioxyben2yl (+)-i7j ,/n7 j -chrysanthemate, and dimethrin [70-38-2] 2,4-dimethylben2yl (+)-i7j ,/n7 j -chrysanthemate. These have alimited spectmm of insecticidal activity but are of very low mammalian toxicity, ie, rat oralLD s >20,000 mg/kg. 

Quinones of various degrees of complexity have antibiotic, antimicrobial, and anticancer activities, eg, a2iddinornitosene [80954-63-8] (36), (-)-2-methyl-l,4-naphthoquinone 2,3-epoxide [61840-91 -3] (37), and doxombicin [23214-92-8] (adriamycin) (38) (see Antibiotics Chemotherapeutics, anticancer), ah of these natural and synthetic materials have stimulated extensive research in synthetic chemistry. 

The third and newest modified natural mbber available is epoxidized natural mbber (ENR). This modification was actually discovered as early as 1922 (50), although the elimination of ring opening and side reactions to give a purely epoxidized material took another 50 years or so to achieve (51). The resulting polymer is a new material, with properties totally different from natural mbber, as iadicated ia Table 5. 

Epoxidized natural mbber is stiU a strain crystallising mbber and therefore retains the high tensile strength of natural mbber. However, as can be seen from Table 5, ia other respects they have very Httie ia common. The epoxidation renders a much higher dampiag mbber, a much-improved resistance to oil swelling (iasofar as a 50 mol % modified natural mbber has similar oil resistance to a 34% nitrile mbber), and much-reduced air permeabiUty. This latest form of modified natural mbber therefore widens the appHcations base of the natural material and enables it to seek markets hitherto the sole province of some specialty synthetic mbbers. 

Table 5. Physical Properties of Black-Filled Epoxidized Natural Rubber ...

A few natural products with oxirane rings fused to five-membered rings are known. These include the antibiotic methylenomycin-A (82) (79H(13)353, 79JOC4210,80JA3904, 81CC714) and the truly remarkable fungal metabolite trichoviridine (83), which appears to be the first example of an isocyanide epoxide (76CPB832). 

The boron trifluoride-ether complex has been employed mainly in the opening of 5,6-epoxides. This reaction was first studied by Henbest and Wrigley and affords products depending on the nature and stereochemistry of the... 

The second C-C bond forming step (step C), while occurring after the first irreversible ee determining step (step B), can affect the observed enantioselective outcome of the reaction. If the radical intermediate collapses without rotation (k3 Ict, k5 ke), then the observed ee would be determined by the first C-C bond forming step (ki vs. k2), that is the facial selectivity (Scheme 1.4.6). However, if rotation is allowed followed by collapse, then the rate of both trans pathways (Ic and k ) will proportionally effect the observed ee of the cis epoxide (ks vs. ks). Should bond rotation be permissible, the diastereomeric nature of the radical intermediates 9a and 9b renders the distinct possibility of different observed ee s for frany-epoxides and dy-epoxides. 

Although the limited examples of AE reactions on 2,3Z-substituted allyl alcohols appear to give product epoxides in good enantioselectivity, the highly substituted nature of these olefins can have a deleterious effect on the reactivity. For example, Aiai has shown that the 2,3E-substituted allyl alcohol 30 can be epoxidized with either (-)-DET or (+)-DET in good yields and enantioselectivity. However, the configurational isomer 32 is completely unreactive using (-)-DET, even after a 34 h reaction time. 

Desymmetrization of meso-bis-allylic alcohols is an effective method for the preparation of chiral functionalized intermediates from meso-substrates. Schreiber et al has shown that divinyl carbonyl 58 is epoxidized in good enantioselectivity. However, because the product epoxy alcohols 59 and 60 also contain a reactive allylic alcohol that are diastereomeric in nature, a second epoxidation would occur at different rates and thus affect the observed ee for the first AE reaction and the overall de. Indeed, the major diastereomeric product epoxide 59 resulting from the first AE is less reactive in the second epoxidation. Thus, high de is easily obtainable since the second epoxidation removes the minor diastereomer. 

The ease with which thiophenes are formed in the reaction of acetylenic epoxides " and of polyacetylenes with hydrogen sulfide is of great interest in connection with the biosynthesis of the naturally occurring thiophenes (cf. Section VIH,A) and also of preparative importance. 2-Methyl-l,2-oxido-5-hexene-3-yne (56) in water containing barium hydroxide reacts with HzS at 50°C to give 4-... 

The Sharpless epoxidation is one of the most important of the newer organic reactions. Although limited to allylic alcohols, it has found wide application in natural product synthesis. 

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