Indole quinones

FIGURE 7.16 Trapping of the phosphate of 5 -dGMP by the pyrido [1,2-a] indole quinone methide. The 13C-NMR shows most trapping with ring retention, labeled pyrido, with trace amounts of ring expansion, labeled azepino. ... 

FIGURE 7.18 pH-rate profile for the disappearance pyrrolo[l,2-a]indole quinone methide. 

TABLE 7.1 Results of Screening of the Pyrido[l,2-a]indole and the Pyrrolo[l,2-a] indole Quinones (Structures Shown in Scheme 7.18)... 

In vivo studies were carried on the aziridinated cyclopent[Z ]indole quinone out before it was discovered that the aziridinyl ring did not participate in DNA alkylation. The results in Fig. 7.22 for the B16 melanoma syngraft model reveal that there was substantial reduction of tumor mass at 3 mg/kg. However, toxicity (animal deaths) became apparent at 5 mg/kg. On the other hand, human lung cancer xenografts in SCID (severe combined immunodeficient) mice were reduced to 50% mass with 3x1 mg/kg doses without any animal deaths. 

Oxidation of the protected 5-aminoindole 129 with Dess-Martin periodinane (DMP) produced the indole-quinone 130. This methodology was employed in a new total synthesis of the Actinomycetes metabolite BE-10988 (131), which is a promising topoisomerase II inhibitor <02JA2221>. 

Enzymes present in melanosomes synthesize two types of melanin, eumelanin and pheomelanin. Figure 2 illustrates the proposed biosynthetic pathways of eumelanin and pheomelanin. The synthesis of eumelanin requires tyrosinase, an enzyme located in melanosomes. Tyrosinase catalyzes the conversion of tyrosine to dopa, which is further oxidized to dopaquinone. Through a series of enzymatic and nonenzymatic reactions, dopaquinone is converted to 5,6-indole quinone and then to eumelanin, a polymer. This polymer is always found attached to proteins in mammalian tissues, although the specific linkage site between proteins and polymers is unknown. Polymers affixed to protein constitute eumelanin, but the exact molecular structure of this complex has not been elucidated. Pheomelanin is also synthesized in melanosomes. The initial steps in pheomelanin synthesis parallel eumelanin synthesis, since tyrosinase and tyrosine are required to produce dopaquinone. Dopaquinone then combines with cysteine to form cysteinyldopa, which is oxidized and polymerized to pheomelanin. The exact molecular structure of pheomelanin also has not been determined. 

The use of radical cyclizations (see Section 3.02.2.7) in the synthesis of intermediates to biologically active indole-quinones was illustrated by the conversion of compound 956 (n = 2, R = BnO, = MeO) into the indolequinone 1206 by hydrogenolytic removal of the benzyl group followed by oxidation with Fremy s salt (Equation 273) <1997J(P1)2639>. 

Melanins are classified according to their chemical structure into the insoluble black eumelanins (poly-5,6-indole quinones) and the alkali-soluble red phaeomelanins (polydihydrobenzothiazines). Nicolaus (5) includes another group, the homoaromatic phenolic allomelanins (per-... 

An indole quinone unit A reduced indole quinone unit... 

Similar to the 2-vinylindole species, the 3-vinylindole derivatives have also been extensively used in synthesis, due to their ability to take part as the 47t component in Diels-Alder reactions with various dienophiles. WhUe some of the work in this field has involved structurally simple 3-vinylindole species, bicyclic structures such as biindoles, indole-quinones, and indole-maleimides have also been used as the 47t components. 

Catecholamine 2, o-quinone 3, leucoaminochrome 6, 5,6-dihydroxyindole 2, 5,6-indole quinone ... 

Melanins high molecular mass, amorphous polymers of indole quinone, empirical formula (CgHjNOj), containing 6-9% nitrogen. M. are natur-... 

The first and second steps are intimately associated the mechanism is discussed in Chapt. X-7. Ring closure to indole, an addition to the quinonoid system, takes place spontaneously and so probably does the polymerization of the indole-quinone in the positions indicated. Melanin seems to retain several radical positions. 

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