Main observation and conclusion The new racemic and dimeric indole alkaloids with the characteristic cyclopenta[b]indole backbone, (+)- and (-)-spondomine (1a/1b), were isolated from a cultured sponge Tedania anhelans. A semi-synthesis was employed to obtain 1a/1b and the other four stereoisomers 1c-1f. Their structures were determined by spectroscopic analysis, single-crystal X-ray, and quantum chemical calculations. Six stereoisomers differ in bioactivity according to their absolute configurations. Especially, (+)-spondomine (1a) displayed cytotoxicity against the K562 cell line and exhibited stronger Wnt and HIF1 dual signaling inhibitory activity at 5 mu mol/L than the positive control, which offers an exciting starting point for further investigations. All stereoisomers significantly promoted angiogenesis and showed moderate anti-inflammation in zebrafish. A quantum chemical calculation and deuteration experiment were applied to unveil the reaction mechanism which guides the synthesis of the target compounds.