Pyrazino indole-1,4-diones

Reduction of the N(ll)=C(lltf) double bond of l,4-dihydro-2//-pyrazino[2,l-A quinazoline-3,6-diones 30 (R1 = indol-3-ylmethyl R2 = Me) and 31 (R1 = CH2-C6H4-C1- z Rz = Me) was effected with NaBH4. While the m-diastereomer, 30, retained its configuration, the /razw-diastereomer, 31, epimerized during the reaction. <1999JOC7233>. 

Although 7,14-dihydroxy-6H,13H-pyrazino[l,2- 4,5-,T]bisindole-6,13-dione can jn pr ncipie exist in two tautomeric forms of the dihydroxy compound 39 and the diketo form 40, only the dihydroxy is observed <2003OBC3396>. Presumably this is due to the enolizable 1,3-dicarbonyl moieties and the formation of the indole ring, therefore leading to aromaticity and a net overall stabilization. 

Table 1 Selected (6R-fran5 )-6-(l,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-pyrazino[l, 2, l,6]pyrido[3,4-b]indole-l,4-dione derivatives their and corresponding physical properties. H NMR data supplied by author...

P,12aP)-2,3,6,7,12,12a-Hexahydro-2-methyl-6-(3,4-methylenedioxy-phenyl)pyrazino[2, l 6,l]pyrido[3,4-fc]indole-l,4-dione. 

Bisdethiobis(methylthio)gliotoxin 592 was heated in dioxane at 70°C for 2 hr in the presence of DBU, to afford a mixture of compounds 593-595 (86CPB340). Under similar conditions pyrazino[l,2-o]indole-l,4(2f/,3//)-dione 597 was obtained from gliotoxin 596. 

Fig. 8. Chemical structure of tadalafil (6-benzo[1,3]dioxol-5-yl-2-methyl-2,3,6,7,12, 12a-hexahydro-pyrazino[1, 2 1,6]pyrido[3,4-b]indole-1,4-dione). Cocrystal structure of PDE5 and tadalafil (PDB ID 1UDU) with the interaction with the conserved Gln817 is shown.

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