Synthesis of 6-amino acid substituted 4,6,7,12-tetrahydro-4-oxoindolo[2, 3-a]quinolizines

In the presence of Na2CO3 (1S, 3S)- and (1R, 3S)-1-(2,2-dimethoxyethyl)-2-( 1,3-dioxobutyl)-3-(1,3-dioxobutyl)oxymethyl-1,2,3,4-tetrahydrocarboline (1) were transformed into (1S, 3S)- and (1R, 3S)-1-(2,2-dimethoxyethyl)-2-(1,3 -dioxobutyl)-3-hydroxymethyl-1,2,3,4-tetrahydrocarboline (2) which were cyc lized to (6S)-3-acetyl-6-hydroxymethyl-4,6,7,12-tetrahydro-4-oxoindolo[2, 3 -a]quinolizine (4), via (6S, 12bS)- and (6S, 12bR)-3-acetyl-2-hydroxyl-6-hy droxymethyl-1,2,3,4,6,7,12,1 2b-octahydro-4-oxoindolo[2,3-a] quinoline (3). (6S)-4 was coupled with Boc-Gly, Boc-L-Asp (beta-benzyl ester), or Boc-L-G ln to give 6-amino acid substituted (6S)-3-acetyl-4,6,7,12-tetrahydro-4-oxo indolo[2,3-a]quinolizines 5a, 5b, or 5c, respectively. After the removal of Boc from (6S)-5a (6S)-3-acetyl-6-glycyl-4,6,7,12-tetrahydro-4-oxoindolo[2, 3-a]quinolizine (6) was obtained. The anticancer activities of (6S)-5 and ( 6S)-6 in vitro were tested.