Epoxy lactones

The opening of the epoxide in the cij-decalin 24 by acetic acid leads exclusively to the hydroxyacetate 25 (through a kinetically controlled rrani-diaxial opening) rather than to the wanted diastereomer 26 (c/ the stereochemistry of the "southern" part of reserpine). To obtain the correct diastereomer the epoxy-lactone 22 is first formed (Scheme 8.6). Thus the conformation of the cij-decalin system, and therefore that of the substituents, is reversed. The kinetic tran -diaxial opening of the epoxide occurs in a regio- and stereoselective manner to afford compound 28 in which the substituents have the correct position and configuration (a-OH, P-OAc),... 

TMSCl as internal electrophile. Otherwise, only dimerization was observed. The diastere-omeric epoxy lactone 195 undergoes mainly oligomerization under the same conditions. 

Epoxidation of 47 using buffered m-CPBA led to a-epoxy lactone 48 in 60% yield. The corresponding P-epoxy isomer was also isolated in 10-20% yield but could be readily separated from a-epoxy isomer 48. The relative stereochemistry of 48 was assigned using nOe experiments. 

It is noteworthy that stereochemical control of the two new stereogenic centers at C4a and Cl2b ultimately stems from the stereochemistry at Cl through the intramolecular Diels-Alder reaction. Hence, an optically pure 46 should lead to an enantioselective preparation of a-epoxy lactone 48, thereby ultimately leading to an enantioselective synthesis of arisugacin A [1], LAH reduction of ( )-a-epoxy lactone 48 led to epoxy diol 49 in 78%... 

DCC/DMAP mediated esterification of 2-butynoic acid using (+)-(/ )-89 followed by intramolecular Diels-Alder cycloaddition of the resulting ester in refluxing n-decane [cone. 0.07 M] provided the tricyclic lactone (+)-47 in 60% overall yield [Scheme 21]. Epoxidation of (+)-47 using m-CPBA led to P-epoxy lactone (+)-48 in 64% yield. The P-epoxy lactone (+)-48 is highly crystalline, unlike the racemic form. 

Hyd roxybuty rolactone Starch 3-Hydroxytetrahydrofuran, 3-aminotetrahydrofuran, epoxy-lactone, furan, pyrrolidone, tetrahydrofuran Werpy and Petersen 2004... 

Alkaline hydrogen peroxide reacts with a jS-unsaturated ketones by a different reaction sequence, exemplified by the behaviour of "A-nor-testosterone 27) [7 ]. The reagent first converts the steroid into the corresponding epoxy-ketone 28) by the mechanism discussed on p. 201, and only then brings about a Baeyer-Villiger oxidation of the ketone function to give the epoxy-lactone (29) as the major product. 

D-Glucose ([52], Fig. 9) has served as an intriguing educt for preparation (31) of the Corey lactone equivalent [59] (32). The iodo compound [53] was readily available from glucose in four steps. Reductive fragmentation, induced by zinc in ethanol, gave the unsaturated aldehyde [54]. Reaction with N-methylhydroxylamine was followed by a spontaneous nitrone cycloaddition to provide the oxazolidine [55]. Catalytic reduction of the N-O bond was accompanied by the unexpected loss of tosylate and aziridine formation. Olefin formation from [56] via the N-oxide and chain extension gave acid [57]. lodolactonization and tri-n-butyltin hydride reduction in the standard fashion led to lactone [58]. After saponification of the benzoates, stereoselective epoxide formation gave epoxy lactone [59]. 

Tetranortriterpenoids.—The structure of sendanin (72), from the bark of a Japanese variety of Melia azedarach, has been confirmed by AT-ray analysis. The novel enol-ether (73) has been isolated from the heartwood of Khaya anthotheca along with 11/3- and lla-acetoxyazadirone (74) and (75). Zinc-copper couple is a very convenient reagent for reduction of epoxides, a,/S-epoxy-lactones, a/S-unsaturated ketones, and a-ketols. The full details of the X-ray analysis of prieurianin have appeared. " ... 

In order to craft the lactone ring, 38 was oxidized to 40 under Swem conditions in a prelude to intramolecular 1,4-addition of the hemiacetal anion [20] formed via nucleophilic attack by methoxide ion at the aldehyde site. With the availability of acetal 41, it became necessary to consider carefully whether to elaborate the epoxy lactone segment in advance of, or subsequent to, introduction of the a,p-unsaturated ester subunit. Since the latter option was considered more workable, 41 was transformed into the enol triflate and subjected to palladium(II) catalyzed methoxycarbonylation [21]. This methodology allowed for proper homologation of 42 to 43, and subsequent conversion to 44, in totally regiocontrolled fashion. 

A very weak triplet of bands at 275.5, 268 and 263 nm are observed for the aromatic ring absorption in Nic-1 (90) due to the dissymmetric environment and 224 nm for side chain epoxy lactone. 

This method has attracted little attention but was a key reaction used by Tishler and co-workers in a total synthesis of the antibiotic cerulenin (4), which contains a sensitive 4-keto-2,3-epoxy amide system. Thus the.butenolide 1 undergoes selective epoxidation with sodium hypochlorite in pyridine to give the hydroxy acid a, which lactonizes on warming to the epoxy lactone 2. Ammonolysis followed by oxidation with Collins reagent gives ( )-cerulenin (4). 

Oxidation of a I,4-di to a lactone (6, 512). The epoxy diol 1 is oxidized by AgaCOa-Celite (15 equiv.) in refluxing benzene to the epoxy lactone 2. The reaction was used in a total synthesis of f/-cerulenin (4), an antibiotic and also an inhibitor of lipid synthesis, The aminolysis of 2 gives the amide alcohol 3 in almost quantitative yield. The last step in the synthesis is oxidation with pyridin-ium chlorochromate. ... 

Methyl 2Z,5-hexadienoate (126) undergoes cyclization to / S-parasorbic acid when treated with polyphosphoric acid. Torssell and his co-workers employed the substrate thus obtained for a new series of sugar synthesis. OL-Desosamine was synthesized in an essentially similar way to that described above. Analogously, DL-chalcose (127, 4,6-dideoxy-3-0-methyl-DL-xy/o-hexopyranose), was obtained, that is, by oxirane ring opening in racemic epoxy-lactone 122 with methanol in the presence of p-toluene-sulfonic acid. 

The lessons learned from the abortive experiments in Scheme 12 were invaluable to Kozikowski and co-workers in developing a slate of do s and dont s for the final strategy (Scheme 13). Most notably, it transpired that the a,P-epoxy lactone C16 (c.f. C9, Scheme 12) underwent classical reductive elimination with zinc in acetic acid to give the P-hydroxy lactone C17, and cyclohexylidenation, followed by oxidation then led to the actinobolin skeleton in CIS. Final processing to give actinobolin hydrochloride now proved to be uneventful. 

Figure 3.42 Diastereoisomers of the epoxy lactone structure proposed for epoxyrollins A and B, and isolated diepoxy- and triepoxy-acetogenins.

A key element in any contemplated route to S-3-P or EPSP is a method for distinguishing between the various hydroxyl groups of the shikimate nucleus. We envisaged accomplishing this by the sequence depicted below, in which the three ring oxygens of the epoxy lactone 1 would be sequentially unmasked and protected or derivatized. 

After silylation of epoxy lactone 1 and opening to the epoxy ester 18, we expected that application of Ganem s procedure for the introduction of the enolpyruvyl side chain would afford an intermediate appropriate for synthesis of EPSP. Unfortunately, the epoxide functionality is incompatible with the rhodium-catalyzed diazomalonate insertion reaction and the desired intermediate 19 is not obtained. The major product appears to result firom deoxygenation of the epoxide. 

The dihydrocarvone can also be oxidized to an epoxy lactone, 7-methyl-4-(2-methyloxiran-2-yl)oxepan-2-one, with mCPBA and subsequently be used as bifunctional monomer and crosslinker in ROPs. Homopolymerizations using benzyl alcohol as the initiator and either diethyl zinc or tin(ll) 2-ethylhexanoate as the catalyst produce only low molecular weight polyesters (<2.5 kg/mol). Copolymerizations with s-caprolactone give flexible crosslinked materials [103]. 

These furan endoperoxides are valuable building blocks for the synthesis of di- and tetrahydrofuran derivatives, e.g., bis-epoxides, epoxy lactones, ene diones, cis-diacyloxiranes, enol esters, butenolides, and others. Furthermore, the primary [4 + 2]-cycloadducts may rearrange into 1,2-dioxetanes or 1,2-dioxolenes. ... 

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