Phenoxazine ring

Dactinomycin Dactinomycin, 2-amino-l,9-bis-(2,9-diisopropyl-6,10,13-trimethyl-l,4,8,ll,14-pentaoxo-7-oxa-3,10,13-17a-tetraaza-5-bicyclo[14.3.0]nonadecylcarbamoyl)-4,6-dimethyl-3//-phenoxazin-3-one (30.3.1), is one of the first antibiotics isolated from a liquid culture of microorganisms of the family Streptomyces parvulus [80-87]. It is a chromonopeptide with a phenoxazine ring and two cyclic polypeptides joined to the carboxyl group at position 2 and 9 of the phenoxazine ring. 

Derivatives of long established fluorescent dyes based on the phenoxazine ring system, such as the cationic Nile Blue (3.25a) 627 nm, and the neutral Nile Red... 

An ester linkage joins the methylvaline residue of the peptide to the side-chain hydroxyl of threonine. Two cis peptide linkages are present. Ignoring the obvious asymmetry of the phenoxazine ring, actinomycin possesses approximate twofold symmetry. 

Actinomycin D has been clinically used for the treatment of many cancers and is known to be a DNA intercalator. The structure of actinomycin D is based on a phenoxazine ring bound to two cyclic pentapeptides [33]. The presence of the phenoxazine ring in the structure of actinomycin D suggests that phenoxazine derivatives may possess anticancer activity. Phenoxazine derivatives are known to be effective multidrug resistance (MDR) modulators in cancer cells [34], potent inhibitors of Akt signaling in cells [35], inhibitors of human plasma cholinesterase [36], and photo-chemotherapeutic agents in cancer cells [37]. Recent studies also show that the relatively water-soluble phenox-azines, such as 2-amino-4,4a-dihydro-4a,7-dimethyl-2H-phenoxazine-3-one and 2-aminophenoxazine-3-one, exert antitumor effects on various cancer cells in vitro and in vivo. [38]. We have investigated 24 phenoxazines [23,39] (Fig. 4). 

Even before the first synthesis of phenoxazine—reported in 1887 by Bernthsen1—two dyestuffs with the phenoxazine ring system, Meldola s blue and gallocyanine, were commercially available. After its discovery, however, the chemistry of the phenoxazines lay dormant for nearly half a century. Only during the last 10 years has this class of compound aroused renewed interest, as evidenced by the discovery of naturally occurring and biologically active phenoxazines. 

A different phenoxazine ring closure has been effected with 2,2 -dimethoxydiphenylamines.21,27 2-Acetamido-3,5-dimethoxytoluene... 

From the available data we may conclude that the reactivity of the carbon atoms of the phenoxazine ring during electrophilic substitution decreases in the following order 3(7) 1(9) 2(8) 4(6). 

Mention should be made of oxazine dyes, used also as biological stains, which are oxidized phenoxazine derivatives containing suitable auxochromic groups. A detailed treatment of these dyes, however, is beyond the scope of this review. Most of the industrial phenoxazine dyes are derived from benzophenoxazines (e.g., Meldola s blue) or from more complex ring systems containing the phenoxazine residue (triphendioxazine dyes).3,118 The long-known dyestuffs orcein and litmus which are prepared by the action of ammonia on certain lichens, and may also occur accidentally in nature, are both based on the oxidized phenoxazine ring system as shown by Musso and co-workers.119... 

The chromophores of some of the peptide antibiotics may also be synthesized from amino acids. Thus the phenoxazine ring of actinomycin originates from tryptophan . 

Sodium hydroxide Phenoxazine ring—Turpin reaction... 

Phenothiazine derivatives, Friedel-Crafts ketone synthesis 17, 879 Phenoxazine ring 17, 328 Phenoxazines via formamides 17, 564... 

Tryptophans, synthesis 18, 965 Tungstic acid 18, 142 Turpin phenoxazine ring closure 17, 328... 

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