Isoalloxazines, methylation

Isay reaction, 2, 79-80 3, 259 Ismelin 7, 656 Isoalloxazine oxidation states, 1, 252 Isoaminopterin synthesis, 3, 327 Isoarsindolines, 1, 543-544 Isoarsinoline, tetrahydro-synthesis, 1, 552-553 stability, 1, 552 Isoascorbic acid structure, 4, 552 ( )-IsoavenacioIide synthesis, 1, 416 Isoazapenem synthesis, 1, 465 Isobacteriochlorin synthesis, 4, 419 Isobacteriochlorin, dimethyl-biosynthesis, 1, 105 Isobacteriochlorin, methyl-biosynthesis, 1, 105 Isobacteriochlorin, trimethyl-biosynthesis, 1, 105 Isobarbituric acid Mannich reaction, 3, 71 synthesis, 3, 133... 

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. 

Flavin-containing enzymes are known as flavoproteins and, when purified, normally contain their full complements of FAD or FMN. The bright yellow color of flavoproteins is due to the isoalloxazine chromophore in its oxidized form. In a few flavoproteins, the coenzyme is known to be covalently bonded to the protein by means of a sulfhydryl or imidazole group at the C-8 methyl group and in at least one case at C-6. In most flavoproteins, the coenzymes are tightly but noncovalently bound, and many can be resolved into apoenzymes that can be reconstituted to holoenzymes by readdition of FAD or FMN. 

Covalent addition at the 10a- and 9a-positions are not likely since the 10-(2, 6 -dimethylphenyl) (I) and 5-ethyl-10-(2, 6 -dimethylphenyl) (II) isoalloxazines behave as ordinary flavins in all the reactions described in this chapter. With these analogues, the 2 - and 6 -methyl groups shield the 9a- and lOa-positions from nucleophilic attack. For instance, the 10a- and 4-positions are opened on alkaline hydrolysis of N(3)-substituted isoalloxazines (23). In the case of I, hydrolysis only occurs at the 4-position because the lOa-position is shielded. 

Examples for mechanism A include many vitamin antimetabolites which are metabolically converted to the corresponding coenzyme-analogues in the latter form, they act as enzyme inhibitors. Thus, 4-deoxypyridoxine 13b) and 6-chloro-7-methyl-9-ribityl-isoalloxazine (7/), classical antimetabolites of the... 

G [139], These widths correlate with the optical spectra of the radicals semiquin-ones with a 19 G linewidth have pronounced absorption between 550 and 650 nm and appear blue those with a 15 G linewidth (Fig. 8a) have spectra with peaks between 485 and 370 nm and appear red. The additional width of the 19 G spectrum is due to an exchangeable proton it has been shown that the linewidth decreases to 15 G in DjO solutions. Experiments on model compounds [141] indicate that the blue type of radical is a neutral semiquinone with the proton on N(5) of the isoalloxazine ring (9), and that the red species is either the semiquinone anion or the neutral 0(4)-enol tautomer. Covalently bound semiquinones have ESR spectra that are distinctly narrowed [142-144], having a width of around 12 G (Fig. 4b). The reason for this is that the covalently bound flavins lack a methyl group at C-8, which when present makes a significant contribution to the total linewidth. 

The disodium salt of 7-nitroso-8-hydroxyquinoline-5-sulphonic acid (Na2L) reacts with Cu " to form CuL,H20. Cu(C10 )2 reacts with 10-methyl-isoalloxazine (L) and aqueous formic acid to form [CuL2](C104)2,4H20, the structure of which is shown as (214). The complex serves as a model compound for metal-flavin enzymes and controverts earlier suggestions that... 

The binding of a flavin prosthetic group to hepatic monamine oxidase has recently been reported to involve a thiol . FAD is linked as a thioether formed between a cysteine and a methyl substituent on the dimethyl isoalloxazine. While binding is generally conceived to be a reversible process and these cases must be viewed as an extreme, they do provide clear examples of the general concept. 

The ring system is substituted in the positions 2 and 4 by hydroxy groups and in the positions 6 and 7 by methyl groups. The 2,4-dihydroxylated benzopteridines are called isoalloxazines. 

The mixture of b-ethyl-y-methyl- and 5-methyl-6-ethyl-g-(i -D-ribityl)isoalloxazine referred to in ref. 39 was later purified by frequent recrystallizations from water. 

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