Isoalloxazine derivatives

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. 

Although this process is unusual, a similar one has been suggested for a 9-substituted isoalloxazine derivative where C=N photoreactivity is also involved. Distinction between the above reaction and abstraction through a disfavored five-membered transition state (but from a far more reactive -CHgOH) has also been made on the basis of deuterium isotope studies. 

Fenner and co-workers have described radicals in which an NH from the pyrazine ring of lumazine or isoalloxazine derived radicals is replaced by S (e.g., 273-275) (cf. Part I Section III,C,5). Cation-radicals were generated by solution of the parent heterocycles in concentrated sulfuric acid or by oxidation by dibenzoyl peroxide in trifluoracetic acid-containing... 

Shinkai et al. (1984) measured the rates for hydrogen transfers from PNPH and MBNAH to isoalloxazine derivatives such as 48 and tetra(0-acetyl)riboflavin (49). A difference in the rate constant due to the chirality on PNPH and 48 was observed in the presence of a large excess of magnesium perchlorate in acetonitrile solution, as shown in Table 28. Such a difference was not observed when the reaction was carried out in aqueous solution, with low concentration of Mg(II) in acetonitrile, nor in the absence of Mg(II). Thus, in this system, Mg(II) is important as a bridge between the two reactants at the transition state of asymmetric hydrogen transfer. 

Among the flavins, or isoalloxazine derivatives, one finds an important natural derivative of this type, it is lactoflavin— more commonly known as riboflavin. Chemically, it is 6,7-dimethyl-9-D-ribityl-isoalloxazine. It is present in a combined state in a large number of animal and vegetable tissues. Like the flavins in general, riboflavin is soluble in water, giving a... 

Riboflavin is an isoalloxazine derivative, i.e. a pteridine ring with a benzene ring fused on to it. The side chain is a Cs-polyhydroxy group. Note that this is not an N-glycoside of ribose, but rather a derivative of ribitol, a pentahydroxy compound. The systematic name is 6,7-dimethyl-9-ribityl-isoalloxazine ... 

Riboflavin is an isoalloxazine derivative. Its chemical properties have already been discussed in Chapt. VI-4. It occurs in bound form in most foods as flmin mononucleotide (FMN) or flavin-adenine dinvdeotide (FAD), or in flavoproteins. Milk alone contains free riboflavin. 

Berezovskii, V. M., L. S. Tul chinskaya, and N. A. Polyakova Alloxazine and Isoalloxazine Derivatives. XIII. Synthesis of 7-Aminoalloxazine, 7-Aminodimethyl-riboflavin, and their Derivatives. Zh. Obsh. Khim. 35, 673 (1965). 

Oxidation of P-nicotinamide adenine dinucleotide (NADH) to NAD+ has attracted much interest from the viewpoint of its role in biosensors reactions. It has been reported that several quinone derivatives and polymerized redox dyes, such as phenoxazine and phenothiazine derivatives, possess catalytic activities for the oxidation of NADH and have been used for dehydrogenase biosensors development [1, 2]. Flavins (contain in chemical structure isoalloxazine ring) are the prosthetic groups responsible for NAD+/NADH conversion in the active sites of some dehydrogenase enzymes. Upon the electropolymerization of flavin derivatives, the effective catalysts of NAD+/NADH regeneration, which mimic the NADH-dehydrogenase activity, would be synthesized [3]. 

Riboflavin is also known as vitamin B2. It contains a complex isoalloxazine ring that humans are unable to synthesize. The complex ring is hooked onto a live-carbon sugar derivative, ribitol, closely related to the ribose that occurs in RNA. The RDA for adult males is 1.3 mg/day and for adult females 1.1 mg/day. Values decrease with increasing age but increase in pregnancy and lactation. Organ meats, milk, bread products, and fortified cereals are substantial sources of riboflavin. 

Riboflavin (vitamin B2 6.18) consists of an isoalloxazine ring linked to an alcohol derived from ribose. The ribose side chain of riboflavin can be modified by the formation of a phosphoester (forming flavin mononucleotide, FMN, 6.19). FMN can be joined to adenine monophosphate to form flavin adenine dinucleotide (FAD, 6.20). FMN and FAD act as co-enzymes by accepting or donating two hydrogen atoms and thus are involved in redox reactions. Flavoprotein enzymes are involved in many metabolic pathways. Riboflavin is a yellow-green fluorescent compound and, in addition to its role as a vitamin, it is responsible for the colour of milk serum (Chapter 11). 

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. 

However, recent x-ray studies on p-hydroxybenzoate-p-hydroxybenzoate hydroxylase binary complex crystals clearly show the aromatic substrate is bound at the flavin 4a-5 edge and orthogonal to the isoalloxazine plane (29). Unless this binary complex structure is highly misinformative, it can be inferred that in the 02, p-hydroxy-benzoate, enzyme ternary active complex, oxygen transfer is in the 4a,5 region, not the la, 1 region of the bound FAD, which rules out la-OOH derivatives as important oxygenating intermediates for this enzyme. 

A groove (Fig. 13) divides the subunit into two lobes. In a derivative made for crystallographic purposes using NaAu(CN)2, the gold was in a pocket close to the isoalloxazine (Fig. 13). The nicotinamide ring of NADPH is thought to be located in this pocket [60]. The p-hydroxybenzoate binds (hydroxyl inwards, carboxyl towards... 

It is beyond the scope of this chapter to deal in depth with the complex array of radicals deriving from pteridine and isoalloxazine, in particular, those which are derived from naturally occurring pterin and flavin compounds. Accordingly, coverage is restricted to simpler examples and their elementary properties. 

The vast majority of flavoenzymes catalyze oxidation-reduction reactions in which one substrate becomes oxidized and a second substrate becomes reduced and the isoalloxazine ring of the flavin prosthetic group (Figure 1) serves as a temporary repository for the substrate-derived electrons. The catalytic reaction can be broken conveniently into two steps, a reductive half reaction (from the viewpoint of the flavin) and an oxidative half reaction. The flavin ring has great utility as a redox cofactor since it has the ability to exist as a stable semiquinone radical. Thus, a flavoenzyme can oxidize an organic substrate such as lactate by removal of two electrons and transfer them as a pair to a 2-electron acceptor such as molecular oxygen, or individually to a 1-electron acceptor such as a cytochrome. 

The reactive part of FAD is its isoalloxazine ring, a derivative of the vitamin riboflavin (Figure 14.15). FAD, like NAD can accept two electrons. In doing so, FAD, unlike NAD+, takes up two protons. These carriers of high-potential electrons as well as flavin mononucleotide (FMN), an electron carrier related to FAD, will be considered further in Chapter 18. 

---