Oximes glucosinolates

On treatment of trialkylsilyl nitronates 1043 with MeLi, LiBr, or BuLi in THF the resulting nitrile oxide intermediates 1044 afford, in dilute THF solution (R=Me) the ketoximes 1045 in ca 50-60% yield, whereas in concentrated THF solution the O-silylated hydroxamic acids 1046 are obtained as major products [144] (Scheme 7.35). Analogously, the silyl nitronate 1047 reacts with the 2,3,4,6-tetra-O-acetyl-/ -D-glucopyranosyl thiol/triethylamine mixture to afford, via the thiohydroxi-mate 1048, in high yield, a mixture of oximes 1049 which are intermediates in the synthesis of glucosinolate [145] (Scheme 7.35). 

CYP79s in the Biosynthesis of Cyanogenic Glucosides and Glucosinolates 233 The Oxime-Metabolizing Enzyme as Branch Point between the Cyanogenic... 

Molecular Identification of Oxime-Metabolizing Enzyme in Glucosinolate... 

Figure 13.2 Biosynthetic pathways of (A) cyanogenic glucosides and (B) glucosinolates. The CYP79s are assumed to catalyze the same reaction in both pathways. It is not known whether the oxime is oxidized to an aci-nitro compound or a nitrile oxide in the glucosinolate pathway.

Cyanogenic glucosides and glucosinolates are related groups of natural plant products, as both are derived from amino acids and have oximes as intermediates. 

THE OXIME-METABOLIZING ENZYME AS BRANCH POINT BETWEEN THE CYANOGENIC GLUCOSIDE AND THE GLUCOSINOLATE PATHWAY... 

S. alba has been used as a model plant for biochemical studies of the oxime-metabolizing enzyme in the biosynthetic pathway of glucosinolates.33 The major... 

Figure 13.5 Metabolic engineering of oxime-derived natural products in Arabidopsis plants. Up- and downregulation of endogenous as well as exogenous CYP79s provides a powerful tool for alteration of the glucosinolate profiles and introduction of novel glucosinolates, as well as for engineering oxime-derived natural products.

DU, L., LYKKESFELDT, J, OLSEN, C.E., HALKIER, B.A., Involvement of cytochrome P450 in oxime production in glucosinolate biosynthesis as demonstrated by an in vitro microsomal enzyme system isolated from jasmonic acid-induced seedlings oiSinapis alba L, Proc. Natl. Acad. Sci. USA, 1995, 92, 12505-12509. 

Mahadevan reviewed research up to 1973, with respect to the pathways of oxime metabolism in plants, and evaluated a series of aliphatic and aromatic oximes that are precursors for the biosynthesis of plant secondary metabolites (as opposed to basic metabolism products that are essential for cell survival), such as cyanogenic glycosides, glucosinolates and certain phytohormones . Some of these oximes are shown below. 

The enzymes that are involved in the conversion of tyrosine to the aldoximes, 25 and 26 02.105 pj tryptophan , phenylalanine , valine and isoleucine " to the corresponding aldoximes are the multifunction cytochrome P450. CYP79A1, that hydroxylates tyrosine, was isolated from Sorghum bichlor and subsequently cloned". These oximes are the building blocks of plant glucosinolates, 15, and glycosides, 16. 

Arabidopsis cytochrome P450 (CYP83A1, CYP83B1) Conversion of aromatic and aUphatic oximes to glucosinolates 101... 

The oxime, 34, is glycosylated by a UDPG-thiohydroximate glucosyltransferase, and subsequently sulfonated by sulfotransferase to yield a glucosinolate of the type Thus, aldoximes generated by initial oxygenation of amino acids are found to serve as substrates of a wide variety of plant enzymes that act directly at the hydroximino function. 

The antitumor activities of indole and isatin oximes and of furan oximes were studied by several investigators. Furan oximes were found to inhibit DNA, RNA and protein synthesis in lipoid leukemia cells. Derivatives of quinoline oximes were also shown to possess antitumor activity , and glucosinolates, 15, were suggested as cancer-preventive agents . ... 

Glucosinolates such as sinigrin are molecules that consist of a /3-thioglucose moiety, a sulfonated oxime, and a variable side chain derived from various amino acids (Figure 5).43 44 Glucosinolates themselves are not toxic to herbivores and are widely distributed in plant tissues. On the contrary, the enzyme called myrosinase or thioglucosidase is distributed in myrosin cells that do not contain glucosinolates. In the flower stalk of... 

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