E. Caballero et al., Steric and stereochemical effects on the free-radical bromination of tetracyclic and hexacyclic fragments of the MDR inhibitor N-acetylardeemin, TETRAHEDRON, 55(49), 1999, pp. 14185-14198
The bromination of several tetracyclic 3,5a,6,10b,11,11a-bexahydro-2H-pyraz
ino[2', 1'-5,1]pyrrolo[2,3-b]indole-1,4-diones under free radical condition
s was studied. In contrast with literature data for related pyrrolo[a,3-b]i
ndole derivatives, the reaction occurs normally at the 11a position rather
than at the benzylic 10b position and was followed by elimination, leading
to 11,1 la unsaturated derivatives. Compounds with an increased steric hind
rance at 11a afforded B-C ring aromatized derivatives. Hexacyclic derivativ
es of the 7,9a,10,14b,15,15a-hexahydroindolo[3 ".2 "-4',5']pyrrolo pyrazino
[2, 1-b]quinazoline-5,g-dione system showed a behaviour similar to the 'non
-hindered' tetracycles, leading to unsaturated analogues of the natural MDR
inhibitor N-acetylardeemin. Unsaturated ardeemin analogues were also obtai
ned by bromination of 2-(o-azidobenzoyl) derivatives of the tetracyclic sys
tems followed by aza-Wittig cyclization. (C) 1999 Elsevier Science Ltd. All
rights reserved.