The biomimetic total synthesis of potential anti-HIV (-)-isatisine A, a novel alkaloid with an unprecedented fused tetracyclic skeleton, was accomplished in eight steps from indole and known 4,6-O-isopropylidene-protected glucal. The synthetic strategy was inspired primarily by the proposed biogenetic hypothesis that indole C-furanoside would be derived from indole C-glucoside via a ring contractive benzilic acid rearrangement. The biogenetic hypothesis was enabled by model studies: the O-glucoside was converted to O-furanoside via a benzilic acid rearrangement. (C) 2014 Elsevier Ltd. All rights reserved.