The first total synthesis of antiplasmoidal isoindolinone alkaloids, spirocollequins A and B, is described. Their diastereomeric [4.4] spirocyclic lactam core was constructed in a dihydroxylation-spirocyclization sequence from a common 3-hydroxyisoindolinone intermediate. The proposed structures of spirocolle-quins have been supported through the comparison of spectroscopic properties of the synthetic samples with those of natural products as well as single-crystal X-ray diffraction analysis using a synthetic pre-cursor of spirocollequin B.(c) 2022 Elsevier Ltd. All rights reserved.