Lipoxygenase application

The wide applicability of the PK reaction is apparent in the synthesis of pyrroles, for example, 45, en route to novel chiral guanidine bases, levuglandin-derived pyrrole 46, lipoxygenase inhibitor precursors such as 47, pyrrole-containing zirconium complexesand iV-aminopyrroles 48 from 1,4-dicarbonyl compounds and hydrazine derivatives. The latter study also utilized Yb(OTf)3 and acetic acid as pyrrole-forming catalysts, in addition to pyridinium p-toluenesulfonate (PPTS). 

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

The title compound (U-66,858) and analogues are of interest as lipoxygenase inhibitors with potential application to the treatment of asthma and related disorders. 

Hydroperoxides play an important role as oxidants in organic synthesis [56-58]. Although several methods are available for the preparation of racemic hydroperoxides, no convenient method of a broad scope was until recently [59] known for the synthesis of optically active hydroperoxides. Such peroxides have potential as oxidants in the asymmetric oxidation of organic substrates, currently a subject of intensive investigations in synthetic organic chemistry [60, 61]. The application of lipoxygenase [62-65] and lipases [66,67] facilitated the preparation of optically active hydroperoxides by enzymes for the first time. 

As discussed, addition of enzyme active soya flour changes the composition of volatile compounds of white bread. In its practical application as a bread improver component, the soya lipoxygenase isoenzymes are sufficient stable for 5 months to meet the bleaching requirements. 

Certain echinacea constituents have demonstrated anti-inflammatory properties in vitro. Inhibition of cyclooxygenase, 5-lipoxygenase, and hyaluronidase may be involved. In animals, application of Epurpurea prior to application of a topical irritant reduced both paw and ear edema. Despite these laboratory findings, randomized, controlled clinical trials involving echinacea for wound healing have not been performed in humans. 

Another application of lipoxygenase (183) is the hydroxylation of unsaturated alcohols (116) via their adipate monoesters (117) where Ris (CH2)4CH3, CH2CH(CH3)2, CH2C6Hb, (CH2)3C6H5, or (CH2)3C(0)CH3. 

Disturbances in lipid metabolism occur in the skin in psoriasis. Increased phospholipase A2 activity is seen in lesional and nonlesional skin, while phospholipase C activity is elevated in lesional skin.183-184 Increased elongase activity is also observed in psoriatic epidermis. A local increase in AA occurs, and this appears to be preferentially metabolized by the lipoxygenases, resulting in a marked increase in 12-HETE and LTB4, while there appears to be a relative or absolute reduction in metabolism by the COX pathway.185 Leukotriene B4 is a very potent chemoattractant, and topical application causes epidermal hyperproliferation in addition to neutrophil microabscesses.186 A defective transmembranous cell-signaling system is also suggested by elevation of both IP3 and DAG in the psoriatic plaque.187... 

Many other plant enzymes (e.g., lipoxygenases, peroxidases, and oxidases) are able to convert their substrates to more biologically active molecules (e.g., aldehydes, peroxides, epoxides 59,60), which may disrupt insect sensory perception and/or metabolism. However, these enzymes can also depreciate the quality of food so that it is toxic or undesirable to animal and human consumers (12,61), so the application of these enzymes to insect and/or disease resistance is not straightforward. 

Cox-1 and Cox-2 are more closely homologous to each other than to lipoxygenase. The complementary effect - increased formation of prostaglandin E and thromboxanes upon application of lipoxygenase inhibitors - has been substantiated by laboratory findings, but I am not aware of evidence that this has a clinical impact . 

In 1886 the use of malted barley flour was mentioned for use in breadmaking. The enzymes in the malt converted starch into sugars which could serve as yeast substrate during fermentation. Almost 50 years later, the use of a purified enzyme (lipoxygenase) was described for bleaching the cmmb of bread. Since then enzyme usage has become widespread in food applications. 

Table IV. Exploratory applications of plant-derived lipoxygenases for flavor modifications of pollack surimi.

Yotova L, Marinkova D (2008) Application of immobilized lipoxygenase in the biosensors design for afiatoxin Bl. BioPS 08 November 4-5,111.37-III.46... 

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