Allene oxide, formation

A reasonable route for the formation of this racemic cyclopentenone (30) was proposed from 8.R-HPETE (29), which involves the non-enzymatic hydrolysis of an allene oxide (64) intermediate (Scheme 5 ) [86]. Biochemical precedence for these transformations was provided by earlier work with plants [90] and C. 

Additional hypotheses concerning prostaglandin biosynthesis in P. homomalla resulted from isolation of 11R-HETE (76) from the polar lipid fraction [95]. Apparently, 11R-HETE (76) is also a minor product of incubations of arachidonic acid with acetone powder preparations of P. homomalla [95], In this alternate hypothesis (Scheme 8), an 11-hydroxy or 11-hydroperoxy-8,9-allene oxide intermediate is formed from a sequence of oxidations at C8 and Cll. Opening of the allene oxide to a transient C8 earboeation induces eycli-zation with a consequent addition of water to C15. This proposed pathway leads initially to formation of PGE2 (16 or 38), which following acetylation, elimination of acetic acid from Cl 1-12, and esterification, forms the observed major natural product in the coral, 15-acetoxy methyl PGA2 (36 or 54). Notably, if... 

Brash AR, Baertschi SW, Harris TM (1990) Non-cyclooxygenase prostaglandin biosynthesis formation of PGA3 isomers via an allene oxide. In Reddy CC, Hamilton GA, Madyastha KM (eds) Biological oxidation systems, vol 2. Academic, San Diego, p 683... 

The oxidation of allenylsulfonamides 75 is also possible by using DMDO [23], Unlike the corresponding reaction of allenyl acids, oxidation of allenyl sulfonamides usually cannot be stopped after the formation of the allene oxide 76 but proceeds further to the spirodiepoxide intermediate 77, finally giving hydroxypyrrolidinone 78 and hydroxypiperidone 79, respectively (Scheme 17.23). Similarly to y-allenyl alcohols, aldehydes and acids, five-membered heterocycles, e.g. 80, are also formed from y-allenylsulfonamides. In the latter case the reaction can be terminated after the first epoxidation by addition of p-toluenesulfonic acid. 

In connection with the above discussion, formation of 3,3-disubsti-tuted 2 (3 H)-oxepinones (73) in the dye-sensitized photooxygenation of 6,6-disubstituted fulvenes is of special interest. 57>58> The reaction may be pictured in terms of an allene oxide intermediate which, as shown in Scheme 11, isomerizes to a cyclopropanone, followed by intramolecular rearrangement. 

The Woodward-Hoffman rules also predict that in a given cyclization mode a permutation of alkene geometry must be reflected in the configuration of the products. This test is precluded under the normal reaction conditions (acid, light) which would isomerize the dienone double bonds. However, Corey recently reported the formation of a c -disubstituted cyclopentenone from a (Z, )-precursor, derived fiom an allene oxide, which cyclizes via the 2-oxido pentadienylic cation (Section 6.3.8). ... 

Since epoxidation at the vinyl double bond is unproductive, it is desirable to direct reaction on the al-lene moiety. This can be accomplished by taking advantage of the hydroxy-directed epoxidation of allylic alcohols using the t-butyl hydroperoxide/vanadium(V) system.The directing effects of both allylic and homoallylic type hydroxy groups have been examined at both positions of the vinylallene unit. " At the 1-position (64), primary, secondary and tertiary allylic tdcohols are effective, while only primary homoallylic alcohols have bran examined (equation 35). Presumably the directing effect of the hydroxy groups favors formation of the intermediate allene oxide (65). A sample of the compounds prepared by this route is shown in Scheme 32. ... 

Finally, there has been speculation and recent experimental support for the involvement of a Nazarov-type cyclization in the biosynthesis of c/ s-jasmonic acid ° and marine-derived prostanoids. Radiolabel tracer studies have demonstrated Ae intermediacy of 8-HPETE (104) in the biosynthesis of prostanoid intermediate preclavulone A (lO ). This remarkable conversion was proposed to proceed by formation of allene oxide (105) followed by isomerization to (107) via the 2-oxidocyclopentadienyl cation (106 Scheme 41). To demonstrate the chemical feasibility of this proposal, Corey reported the transformation of epoxysilane (108) to, inter alia, the cyclopentenone (111 Scheme 42). The reaction is presumed to involve formation of the allene oxide (109) followed by isomerization to the 2-oxi-dopentadienylic cation (110). Conrotatory closure of (110) is expected to produce the cis isomer of (111) as observed. 

Strong experimental support for the biochemical pathway is provided by the isolation and characterization of the allene oxide (105) by Brash. ° Further, solvolysis of (105) produced (107) along with a-ketols. ° ° The biochemical mechanism for formation of an allene oxide from 8-HPETE remains to be clarified. 

In a similar study, formation of allene oxides has been inferred from the collisional activation (CA) mass spectra of the products from rearrangements of a-methoxy- or thiomethoxyketones in the gas phase <93JCS(P 1)2235). 

Allen PG, Conradson SD, Wilson MS, Gottesfeld S, Raistrick ID (1993) Real time structural electrochemistry of platinum clusters using dispersive XAFS. Mat Res Soc Symp Proc 307 (Applications of Synchrotron Radiation Techniques to Materials Science) 51-56 Allen PG, Conradson SD, Wilson MS, Gottesfeld S, Raistrick ID, Valerio J, Lovato M (1995b) Direct observation of surface oxide formation and reduction on platinum clusters by time-resolved X-ray absorption spectroscopy. J. Electroanal Chem 384 99-103 Allen PG, Shuh DK, Bucher JJ, Edelstein NM, Palmer CEA, Silva RJ, Nguyen SN, Marquez LN, Hudson EA (1996b) Determinations of uranium structures by EXAFS schoepite and other U(VT) oxide precipitates. Radiochim Acta 75 47-53... 

Oxidation of 3-allenic alcohols of the type (1) with Payne s reagent results in formation of 7-lactones (2) probably via an allenic oxide (a). ... 

Since AA is only a minor fatty acid in higher plants, eicosanoids are not of major importance for plant physiology. However, the oxygenation metabolites of linoleic acid and a-linolenic acid, called oxylipins [5,6], do play a role in plant defence reactions, in the formation of phytohormones and in the synthesis of cutin monomers [6,40-43]. Oxylipins constitute a family of lipids that are formed from free fatty acids by a cascade of reactions involving at least one step of dioxygen-dependent oxidation. The biosynthesis of oxylipins proceeds via a large number of metabolic pathways, most of which involve an unsaturated hydroperoxy fatty acid as intermediate (Scheme 10). Conversion of the hydroperoxide via the peroxide lyase pathway, the allene oxide pathway and the recently discovered peroxygenase pathway, leads to a complex pattern of oxidized lipid mediators. 

The last route is important for the formation of jasmonic acid. The action of allene oxide synthase on 13-hydroperoxy linolenic acid initially results in the generation of 12,13-epoxy-octadecatrienoic acid. This unstable epoxide is either chemically hydrolyzed to a- and y-ketols and racemic 12-oxo-phytodienoic acid or, in the presence of allene oxide cyclase (AOC), is further converted to enantiomeric pure 12-oxo-PDA [7]. The ring double bond of PDA is then reduced in a NADPH dependent reaction by 12-oxo-PDA reductase and after shortening of the side chain containing the carboxy group by 3 rounds of fi>-oxidation, the biosynthesis of jasmonic acid is completed. 

Stumpe, M. et al. (2006) Identification of an allene oxide synthase (CYP74C) that leads to formation of alpha-ketols from 9-hydroperoxides of linoleic and linolenic acid in belowground organs of potato. Plant J. 47, 883 896... 

Oxylipins are commonly found metabolites in higher plants and most of them originate from polyunsaturated fatty acid hydroperoxides by enzymatic transformations which have been extensively studied (for recent reviews, see 1,2). Two well characterized enzymes a lyase and an allene oxide synthase were shown to degrade hydroperoxides into compounds of physiological importance since they can ultimately yield fragrances or plant hormones such as jasmonic acid. We have recently reported a new fate for fatty acid hydroperoxides the peroxygenase pathway. It involves two enzyme activities i.e. a peroxygenase and an epoxide hydrolase which lead to the formation of epoxidized fatty acids and their derived dihydrodiols which are relevant to plant defense mechanisms. 

The most recent findings relating to lipoxygenase pathway in plants concern allene oxides, the primary products of enzymatic transformations of fatty acid hydroperoxides. Spontaneous hydrolysis of allene oxides leads to the formation of a- and y-ketols [1]. It has been also found that hydroperoxide dehydrase from flax seeds converts 8-hydroxy-155-hydroperoxy derivatives of arachidonic and eicosapentaenoic acids into a-ketols and prostaglandin A3 analogues [2]. These data allow us to hypothesize formation of ketols of 9-hydroxy derivative of a-linolenic acid. 

Brash AR, Baertschi SW, Harris TM. Formation of prostaglandin. A analogues via an allene oxide. J Biol Chem 1990 265 6705-6712. 

Song WC, Brash AR. Investigation of the allene oxide pathway in the coral Plexaura homomalla formation of novel ketols and isomers of prostaglandin Ai from 15-hydroxyeicosatetraenoic acid. Arch Biochem Biophys 1991 290 427-435. 

Brash, A.R. (1989) Formation of an allene oxide from (8J )-8-hydroperoxyeicosatetraenoic acid in the coral Phxaura homomaUa. J. Am. Chem. Soc., Ill, 1891-1892. 

Tlie thioketone 5-oxide 85, generated from allene 86 and SOCk in situ, decomposes to give the alkene 87. A mechanism, involving the transient formation of the 1,2-dithietane 88 (by dimerization of 85 followed by rearrangement), was proposed (85AGE855). 

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