An acyclic intermediate representing a putative biomimetic precursor of the C28-C40 domain of the novel marine toxin azaspiracid was constructed convergently from C28-C34 and C35-C40 fragments. In studying the assembly of the C28-C34 dioxabicyclo[3.3.1]nonane system via an intramolecular hetero-conjugate addition upon a C34-C36 enone, a stereoselective C-Michael addition intervened to provide a highly substituted cyclohexane. (C) 2001 Elsevier Science Ltd. All rights reserved.