Ergosterol transformations

The photochemistry of all these compounds is of interest with respect to the well-known photochemistry of cyclohexadiene (1.3) derivatives, for instance, the photochemical reactions of 2.4.6-triaryl-cyclohexadien(2.4)-on-ol(2) series of Perst and Dimroth or in a more comprehensive context the photochemical transformation of ergosterol, luniisterol, isopyrocalciferol and pyrocalciferol which were first studied by Windaus and Dimroth and fully investigated by Veluz, Havinga and Dauben... 

Vitamin D is represented by cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2), which are structurally similar secosteroids derived from the UV irradiation of provitamin D sterols. In vertebrates, vitamin D3 is produced in vivo by the action of sunlight on 7-dehydrocholesterol in the skin. Vitamin D2 is produced in plants, fungi, and yeasts by the irradiation of ergosterol. On irradiation, the provitamins are converted to previtamin D, which undergoes thermal transformation to vitamin D. 

The photochemical transformations of ergosterol have been the subject of continuing investigation for almost half a century (130-133). The interrelations among the photoproducts of ergosterol (Formula 317) and subsequent transformation products are summarized below. It has been shown in an elegant investigation that previtamin D2 (Formula... 

Rahier and his co-workers also characterized the activities of a sterol C-4 methyl oxidase (SMO), a 4-carboxysterol-3-hydroxysteroid dehydrogenase/ C-4 decarboxylase (3-HSD/D) and an NADPH-dependent 3-oxosteroid reductase in order to define the steps involved in C-4 demethylation in plants (Pascal et al, 1993 Rondet et al, 1999). Only recently, they have isolated two cDNAs from Arabidopsis thaliana encoding bifunctional 3-HSD/D. Transformation of a yeast ergosterol auxotroph mutant, which lacks 3-HSD/D activity, with either of these cDNAs restored ergosterol biosynthesis in the yeast mutant (Rahier et al, 2006). 

It is an interesting historical fact that the study of the photochemistry of conjugated dienes and trienes was initiated by the discovery of the photochemical transformation of ergosterol to vitamin D—a system... 

Ergosterol (E) and lumisterol (L) bear the same relation to precalciferol (P) and tachysterol (T) as 1,3-cyclohexadiene does to ds- and trans-1,3,5-hexatriene. The details of the photochemical processes in this system have been studied extensively by Havinga and his co-workers. Phosphorescence has not been observed from any of these compounds, while fluorescence has been recorded from E, L, and T. Havinga and Schlatmann have concluded that the photochemical transformations in... 

The tachysterol/ergosterol system continues to attract considerable interest. A typical result has shown that the triols (122) can be transformed on irradiation in ether/THF into Previtamin analogues which are thermally converted into the... 

A group of fungicides that inhibit squalene epoxidation has been developed primarily for use against pathogenic fungi in medicine. Epoxidation of squalene is catalyzed by squalene epoxidase (a flavoprotein) that starts the complicated cyclization of squalene. The squalene-2,3-epoxide formed by this enzyme is further metabolized to a protosterol cation intermediate, which is transformed to either cycloartenol in plants (cycloartenol synthase) or lanosterol (lanosterol synthase). Cycloartenol is the precursor to plant sterols, whereas lanosterol is the precursor of cholesterol and the other sterols in animals, and to ergosterol in plants. 

There are many instances reported in the literature where spectrophotometry has been employed for the determination of reaction rates or for the identification of labile intermediates in the reactions. Isomerization reactions are particularly well-suited for spectrophotometric studies anionotxopic rearrangements of substituted alcohols 8, R,CH(OH)CH — CHR, - RICH = CHCHfOHJRj, photochemical transformation of ergosterol to vitamin Dj 8>70, alkali-catalyzed isomerization of arachidonic acid71, photochemical changes in thioctic acid78 etc. 

Scheme 13.35. A representation of the photochemical electrocyclic transformation between ergosterol (a plant sterol ) and ergocalciferol or vitamin D2 as well as the relationship between A -cholesteroldiene (an animal sterol ) and calciol or vitamin D3.

After absorption, oxysterols react with blood plasma lipoproteins to form complexes that can initiate formation of atherosclerotic deposits in the vascular wall. However, the important oxidation reaction from the physiological point of view is the transformation of provitamins D (ergosterol and 7-dehydrocholesterol) into vitamins D2 and Dj, respectively. 

To provide sufficient amounts of FPP, the yeast pathway starting from acetyl-CoA is up-regulated and the pathway flux through the downstream reactions from FPP to the end-product ergosterol is restricted by repressing the yeast squalene synthase (Erg9). This leads to a substantial accumulation of FPP, which is efficiently converted to amorpha-9,ll-diene by the recom-binantly overexpressed amorphadiene synthase (ADS) from A. annua. A three-step oxidation reaction transforms amorpha-9,ll-diene into artemisinic acid. All steps of the first functional artemisinic acid pathway in... 

A New Mechanistic Scenario for the Photochemical Transformation of Ergosterol An MCSCF and MM-VB Study. 

Vitamin D is composed of a number of related stmc-tures but the two most prominent members of the family are colecalciferol and ergocalciferol, which is formed from ergosterol rather than 7-dehydrocholesterol. Cole-calciferol is transformed into the most active form of the vitamin, 1,25-dihydroxycholecalciferol, by hydroxylation at the 25 position in the liver and finally at the 1 position in the kidneys. 

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