Aromatization lactone

Bromomethyl-3,4-dibromo-3,4-dihydrocoumarin 1 (Fig. 11.4) and its chloro-methylated analogue 2b rapidly and progressively inactivate a-chymotrypsin and also the activities of a series of trypsin-like proteases. A benzyl substituent characteristic of good substrates of a-chymotrypsin was introduced at the 3-position to make inhibition more selective. This substituted dihydrocoumarin 3 irreversibly inhibited a-chymotrypsin and other proteases. These functionalized six-membered aromatic lactones, and their five- and seven-membered counterparts, 3//-benzofuran-2-ones 2a26 and 4,5-dihydro-3//-benzo[b]oxepin-2-ones 2c,27 were the first efficient suicide inhibitors of serine proteases. Their postulated mechanism of action is shown in Scheme 11.2. 

Lactones (cyclic esters) are usually stable toward hydrogenolysis. However, the aromatic lactones contain benzylic C—O bonds and can be hydrogenolyzed. As an example, the hydrogenolysis of an aromatic lactone was performed over Ra-Ni in THF under 4 atm H2 pressure at 50°C for 30 hours.213... 

Berberine can be oxidized by nitric acid to berberidic acid (82), which forms two isomeric monomethyl esters these can be reduced first to the isomeric unsaturated lactones (83) and (84) and further to saturated lactones and to cis- and trans-diols (85). Hydrogenation of berberidic acid diester affords an allo-hexahydro-compound, which is isomerized by base to a normal hexahydro-compound. Oxidation of the lactone (84) with mercuric acetate affords the aromatized lactone (86).95... 

During the course of studies on the microbial production of chiral intermediates for D-pantothenic acid [2,134,135], Shimizu and co-workers found that several micro-organisms, such as Fusarium, Brevibacterium and so on, produce a novel enzyme that catalyzes the hydrolysis of aldonate lactones or aromatic lactones [136, 137],... 

Brevibacterium protophormiae produces a similar kind of lactonase, which hydrolyzes various kinds of aromatic lactones as well as the Fusaruim lactonase, but aldonate lactones are not hydrolyzed. The enzyme hydrolyzes only l-pantolactone D-pantolactone is not a substrate. The relative molecular mass of the native enzyme is 62 kDa, and the subunit molecular mass is 26.5 kDa [137],... 

Reaction with lactones, anhydrides. Canonne et al.1 have observed high stereoselectivity in reaction of 1 with aromatic lactones and anhydrides resulting in the... 

Hundreds of compounds have been identified in the volatile flavor components of processed foods. Hydrocarbons, alcohols, ethers, aldehydes, ketones, acids, acid anhydrides, esters, aromatic, lactones, pyrones, furans, pyridines, pyrroles, n-alkylpyrrole-2-aldehydes, pyrazines, sulfides, disulfides, thiols, thiophenes, thiazoles, trithiolanes, thialdine. ..etc. 

The preparation of a number of medium ring benzoic acid lactones was achieved by treatment of compounds such as VIII/176 with an excess of meta-chloroperoxybenzoic acid in dichloromethane, Scheme VIII/33 [103]. However, this oxidation reaction is not general for the synthesis of aromatic lactones. If the same reaction conditions are used as in the conversion of VIII/176 to VIII/177, the methoxy derivative VIII/178 is not transformed into the corresponding lactone. Instead the cyclic carbonate VIII/183 was isolated in a yield of 50 %. The proposed mechanism of this abnormal reaction is shown in Scheme VIII/33. From model compounds, the methoxyl group in the para-position to the center of oxidation seems to be important for the formation of VIII/183 [103]. The carbonate VIII/183 is unstable in aqueous alkaline medium and decomposes to the spiro compound, VIII/185, Scheme VIII/33 [103]. For an analogous reaction, see ref. [104]. 

An enzyme isolated from F. oxysporum catalyzes the hydrolysis of various aldonate and aromatic lactones (Table 19.1) (Shimizu et al, 1992). The hydrolysis of aldonate lactones proceeds stereospecifically through recognition of... 

Shimizu, S., Kataoka, M., Shimizu, K., Hirakata, M., Sakamoto, K., and Yamada, H. 1992. Purification and characterization of a novel lactonohydrolase, catalyzing the hydrolysis of aldonate lactones and aromatic lactones, from Fusarium oxysporum. Eur. J. Biochem.,209, 383-390. 

We have today a better understanding of the composition of oak of various origins. Oak is a naturally aromatic wood. This is largely due to the presence of a highly aromatic lactone, fi-methyl- -octalactone [1], which is specific to the Quercus genus... 

Photolysis of aromatic lactones and anhydrides, such as naphthalene-1,2-dicarboxylic anhydride (339), gives arynes (in this case 340)1039 as reactive intermediates.1040 Matrix isolation spectroscopy (Section 3.10) then allows their study along with other exotic molecules, which are formed as primary or secondary (photo)products (Scheme 6.150). 

Since the publication of this work Aharoni et al., it has been established that serum paraoxonase (PON1) is a lipo-lactonase, and its preferred substrates are five- and six-membered ring lactones, typically with aliphatic side chains.° °°° °° In the original article, data for trade-offs with the native activity were presented with both the aromatic lactone dihydrocoumarin, and aliphatic lactones. However, more recent works indicated that dihydrocoumarin does not bind PON1 s active site in the same mode as aliphatic lactones.°° "° Thus, the trade-offs presented here are the average values of two aliphatic lactones (i5-valerolactone and and 7-heptanolide). 

In this structure type the cleavage of the labile bonds in ring C by a retro Diels-Alder reaction is dominant, generating two fragments one, the most characteristic, represents the pyrrolidine ring (plus substituents in position 2), and the other (a less abundant fragment) encompasses the aromatic lactone or hemilactone moiety (Fig. 14). A further general and noteworthy feature is the low abundance of the molecular ion in all compounds with a double bond (211). 

Podophyllotoxin is an aromatic lactone that arrests the metaphase activity in the DNA synthesis. 

Elimination of the angular substituent of the diazoketone (75) by treatment with copper, affording the aromatic lactone (80), has been reported. It proceeds presumably through the intermediates (76)—(79). Oxidation of oestrone (81)... 

We found in our laboratory, a novel lactonohydrolase that catalyzes reversible hydrolysis of various lactones including aldonate lactones and aromatic lactones. The enzyme was crystallized from Fusarium oxysporum and characterized. It has been shown that the enzyme hydrolyzes only D-pantoyl lactone, a chiral intermediate for the commercial production of D-pantothenate, in a racemic mixture of pantoyl lactone and that the enzyme is very useful for the optical resolution of racemic pantoyl lactone (Fig. 3)7. When F. oxysporum mycelia entrapped in calcium alginate gel were incubated in 30% solution of DL-pantoyl lactone, almost stoichiometric hydrolysis of D-pantoyl lactone was observed. After repeated reactions for 150 times over 150 days, the mycelia retained more than 90% of their initial activity. A 1,000... 

Lactones loss of a-suhstituents (attached to ether carbon), decatbonylation, for aromatic lactones also double decarbonylation... 

Fragmentation The most prominent reaction is the loss of substituents (or H ) at the 0-bearing C atom, followed by decarbonylation (Am 28), decarboxylation (Am 44, mainly in smaller molecules), and ketene elimination (Am 42). Decarboxylation of M" " is rarely significant. Competing reactions are several kinds of primary ring cleavages. Aromatic lactones show maxima due to two consecutive decarbonylations. 

Molecular ion Usually of low intensity and easily protonated to [M+H]+ in aliphatic lactones abundant in the case of aromatic lactones. 

Lactones are formed predominantly from y-, (5-, and e-hydroxy acids. Most lactones of the aliphatic series are converted easily under the influence of water to corresponding hydroxy acids. For the hydrolysis of aromatic lactones heating with alkalies is necessary. The reactions of lactones with ammonia and phenylhydrazine, which can be used in certain cases for identification purposes, are described in greater detail in a special monograph (134). Aliphatic y-lactones react in benzene solution with thionyl chloride, with the formation of hydroxy acid chlorides, from which suitable derivatives can be prepared (135). 

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