Ribityl riboflavin

In aqueous solution, riboflavin has absorption at ca 220—225, 226, 371, 444 and 475 nm. Neutral aqueous solutions of riboflavin have a greenish yellow color and an intense yellowish green fluorescence with a maximum at ca 530 nm and a quantum yield of = 0.25 at pH 2.6 (10). Fluorescence disappears upon the addition of acid or alkah. The fluorescence is used in quantitative deterrninations. The optical activity of riboflavin in neutral and acid solutions is [a]=+56.5-59.5° (0.5%, dil HCl). In an alkaline solution, it depends upon the concentration, eg, [a] J =—112-122° (50 mg in 2 mL 0.1 Ai alcohohc NaOH diluted to 10 mL with water). Borate-containing solutions are strongly dextrorotatory, because borate complexes with the ribityl side chain of riboflavin = +340° (pH 12). 

Later, a completely different and more convenient synthesis of riboflavin and analogues was developed (34). It consists of the nitrosative cyclization of 6-(A/-D-ribityl-3,4-xyhdino)uracil (18), obtained from the condensation of A/-D-ribityl-3,4-xyhdine (11) and 6-chlorouracil (19), with excess sodium nitrite in acetic acid, or the cyclization of (18) with potassium nitrate in acetic in the presence of sulfuric acid, to give riboflavin-5-oxide (20) in high yield. Reduction with sodium dithionite gives (1). In another synthesis, 5-nitro-6-(A/-D-ribityl-3,4-xyhdino) uracil (21), prepared in situ from the condensation of 6-chloro-5-nitrouracil (22) with A/-D-ribityl-3,4-xyhdine (11), was hydrogenated over palladium on charcoal in acetic acid. The filtrate included 5-amino-6-(A/-D-ribityl-3,4-xyhdino)uracil (23) and was maintained at room temperature to precipitate (1) by autoxidation (35). These two pathways are suitable for the preparation of riboflavin analogues possessing several substituents (Fig. 4). 

Lumazine, l,3-dimethyl-6-phenyl-oxidation, 3, 305 Lumazine, 6,7-dimethyl-8-ribityl-in riboflavin biosynthesis, 1, 93 Lumazine, 6,7-dimethyl-8-D-ribityl-biosynthesis, 3, 320 structure, 3, 277 Lumazine, 6,7-dimethyl-2-thio-reactions... 

Pyrido[2,3-d]pyrimidine, 8-ribityl-as inhibitor of riboflavin synthesis, 3, 260 Pyrido[2,3-(i]pyrimidine, thioxo-reactions, 3, 211... 

Flavins — These are isoalloxazine derivatives methylated at Cg and C-j, with substituents at Ng The most important flavin, riboflavin, has a ribityl gronp (derived from ribitol) at Ng. 

Incorporation of a flavin electron donor and a thymine dimer acceptor into DNA double strands was achieved as depicted in Scheme 5 using a complex phosphoramidite/H-phosphonate/phosphoramidite DNA synthesis protocol. For the preparation of a flavin-base, which fits well into a DNA double strand structure, riboflavin was reacted with benzaldehyde-dimethylacetale to rigidify the ribityl-chain as a part of a 1,3-dioxane substructure [49]. The benzacetal-protected flavin was finally converted into the 5 -dimethoxytri-tyl-protected-3 -H-phosphonate ready for the incorporation into DNA using machine assisted DNA synthesis (Scheme 5a). For the cyclobutane pyrimidine dimer acceptor, a formacetal-linked thymine dimer phosphoramidite was prepared, which was found to be accessible in large quantities [50]. Both the flavin base and the formacetal-linked thymidine dimer, were finally incorporated into DNA strands like 7-12 (Scheme 5c). As depicted in... 

This enzyme [EC 2.5.1.9] catalyzes the conversion of two 6,7-dimethyl-8-(l-D-ribityl)lumazine to produce riboflavin and 4-(l-D-ribitylamino)-5-amino-2,6-dihydroxy-pyrimidine. 

Riboflavin (vitamin Bj) is chemically specified as a 7,8-dimethyl-10-(T-D-ribityl) isoalloxazine (Eignre 19.22). It is a precnrsor of certain essential coenzymes, such as flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD) in these forms vitamin Bj is involved in redox reactions, such as hydroxylations, oxidative carboxylations, dioxygenations, and the reduction of oxygen to hydrogen peroxide. It is also involved in the biosynthesis of niacin-containing coenzymes from tryptophan. 

Riboflavin synthase catalyzes the dismutation of 8-D-ribityl-6,7-dimethyllumazine to form the flavin ring system and the general features of the mechanism of this reaction have been known for some time. Recent X-ray structural studies of the enzyme from archaeal organisms such as methanobacteria have shown that the chemical mechanism of action is similar to that of enzymes from eubacteria and eukaryotes although the structures of the enzymes differ greatly <2006JBC1224>. 

Vitamin Bj (8.44, riboflavin) is a benzopteridine derivative carrying a ribityl (reduced ribose) side chain. It occurs in almost all foods, the largest amounts being found in eggs, meat, spinach, liver, yeast, and milk. Riboflavin is one of the major electron carriers as a component of flavine-adenine dinucleotide (FAD), which is involved in carbohydrate and fatty acid metabolism. A hydride ion and a proton are added to the pyrazine ring of... 

While the mechanism for the formation of (35) has not been determined, an internal oxidation-reduction of the ribityl group (similar to that catalyzed by methylglyoxal synthetase) to afford the free diketone (38) which reacts with a second molecule of (32), appears plausible. In support of this it has been shown (82JA3754) that label from [1-3C]ribose is incorporated at the C-5 of riboflavin (corresponding to the 6-methyl of 33) and not at C-8. 

Riboflavin (vitamin B2) 6,7-dimethyl-9-(D-l-ribityl)isoalloxazine (63), was discovered as a coloring matter in milk in 1879, but its importance was not then realized. Deficiency causes lesions of the eye and of the angle of the mouth. Riboflavin is phosphorylated by adenosine triphosphate (ATP) to give riboflavin 5 -phosphate (flavinadenine mononucleotide, FMN) and then flavinadenine dinucleotide (FAD) (64 R = riboflavin). These function as prosthetic groups in a number of flavoproteins which are dehydrogenation catalysts by virtue of the oxidation-reduction properties of the isoalloxazine system. 

When taken up by the body, riboflavin is converted into its coenzyme forms (Chapter 25) and any excess is quickly excreted in the urine. Urine also contains smaller amounts of metabolites. The ribityl group may be cut by the action of intestinal bacteria acting on riboflavin before it is absorbed. The resulting 10-hydroxyethyl flavin may sometimes be a major urinary product.c d The related 10-formylmethyl flavin is also excreted,0 as are small amounts of 7a- and 8a- hydroxyriboflavins, apparently formed in the body by hydroxylation. These may be degraded farther to the 7a- and 8a- carboxylic acids of lumichrome (riboflavin from which the ribityl side chain is totally missing).6 A riboflavin glucoside has also been found in rat urine.f... 

VITAMIN B2 (Riboflavin). Some earlier designations for this substance included vitamin G, lactoflavin, hepatoflavin, ovoflavin, veidoflavin. The chemical name is 6,7-dimcthyl-9-d-l ribityl isolloxazine. Riboflavin is a complex pigment with a green fluorescence. Riboflavin deficiency frequently accompanies pellagra and the typical lesions of both nicotinic acid and riboflavin deficiency are found in that disease. See also Niacin. 

Flavin adenine dinucleotide (FAD) (fig. 10.8) and flavin mononucleotide (FMN) are the coenzymatically active forms of vitamin B2, riboflavin. Riboflavin is the NI0-ribityl isoalloxazine portion of FAD, which is enzymatically converted into its coenzymatic forms first by phosphorylation of the ribityl C-5 hydroxy group to FMN and then by ade-nylylation to FAD. FMN and FAD are functionally equivalent coenzymes, and the one that is involved with a given enzyme appears to be a matter of enzymatic binding specificity. 

Crude riboflavin, prepared as described above starting with 43.6 g of 2-(o-biphehylazo)-4,5-dimethyl-l-ribityl amino-benzene, is washed with 50 ml of cold ethyl acetate, slurried with 180 ml of methanol at 65°C for thirty minutes. The methanol slurry is cooled to 10°C for thirty minutes, filtered, and the filtered material washed with 40 ml of cold methanol. The methanol washed riboflavin is then slurried with 180 ml of water at 80°C for thirty minutes, the slurry is cooled to 70°C, filtered, and the filtered material is washed with 40 ml of hot (70°C) water. The hot water-washed riboflavin is... 

Pyrazines. In the thirties, the attention on pyrazines was focused on its industrial role in dyes, photographic emulsions and chemotherapy. Its importance in life processes was indicated in its derivative, vitamin B2 (riboflavin, 6,7-dimethyl-9-(l -D-ribityl isoalloxazine). Later,in the midsixties, it was identified in foods and its contributions to the unique flavor and aroma of raw and processed foods attracted the attention of flavor chemists Pyrazine derivatives contribute to the roasting, toasting, nutty, chocolaty, coffee, earthy, caramel, maple-like, bread-like, and bell pepper notes in foods. The reader is referred to the reviews on Krems and Spoerri (88) on the chemistry of pyrazines, and the review of pyrazines in foods by Maga and Sizer (89, 90) Table XVI summaries sensory description and threshold of selected pyrazines. 

Fig. 8.28 Biosynthesis of riboflavin in bacteria. Compounds ArP, 5-amino-6-(ribityl-amino)-2,4-(l /-/,3H)-pyrimidinedione ...

The ribityl moiety is not linked to the isoalloxazine ring by a glycosidic linkage, and it is not strictly correct to caU FAD a dinucleotide. Nevertheless, this trivial name is accepted, as indeed is the even less correct term flavin mononucleotide for riboflavin phosphate. 

Intestinal bacterial cleavage of the ribityl side chain results in the formation of 10-hydroxyethylflavin (an oxidation product of lumifiavin), lumichrome, and 7- and 8-carboxy-lumichromes, which are also excreted in the urine. Some of the lumichromes detected in urine may result from photolysis of riboflavin in the circulation. 

Fo, 35), which is an analog of riboflavin, serves as the business end of coenzyme F420 (36, Fig. 3), whose designation is based on its characteristic absorption maximum at 420 mn. Factor Fo is biosynthesized from the pyrimidine type intermediate 23 of the riboflavin biosynthetic pathway, which affords the pyrimidine ring and the ribityl side chain, whereas the car-bocyclic moiety is derived from the shikimate pathway via 4-hydroxyphenylpyruvate (56, 57). In contrast to the coenzymes described below, deazaflavin-type coenzymes are not strictly limited to methanogenic bacteria and are also found in strepto-mycetes and mycobacteria. 

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