The concise and efficient synthesis of tetrahydroquinoline alkaloids lycibarbarines A−C has been accomplished in four steps from a common intermediate derived from commercially available 2-deoxy-D-ribose and 8-hydroxyquinoline. For the synthesis of the unique tetracyclic spiro-heterocycle skeleton we employed a synthetic strategy that features two key transformations: iodomethyllithium-based homologation of lactone / N-alkylation to access tetracyclic spiro-heterocycle skeleton in one step and one-pot acetonide deprotection, hemiacetal formation, and spirocyclization cascade process. © 2023 Wiley-VCH GmbH.