Macrocyclic furanobutenolide-derived cembranoids (FBCs) are the biosynthetic precursors to a wide variety of highly congested and oxygenated polycyclic (nor)diterpenes (e.g. plumarellide, verrillin or bielschowskysin). These architecturally complex metabolites are thought to originate from site-selective oxidation of the macrocycles’ backbone and a series of intricate transannular reactions. Yet the development of a common biomimetic route has been hampered by a lack of synthetic methods for the pivotal furan dearomatization in a regio- and stereoselective manner. To address these shortcomings, a concise strategy of chemo- and stereoselective epoxidation followed by a kinetically-controlled furan dearomatization is reported. The surprising switch of facial a:b-discrimination observed in the epoxidations of the most strained E-acerosolide versus E-deoxypukalide and E-bipinnatin J derived macrocycles has been rationalized by the 3D-conformational preferences of the macrocyclic scaffolds. The downstream functionalization of FBC-macrocycles was also studied, and how the C-7 epoxide configuration was retentively translated to the C-3 stereogenicity in dearomatized products under kinetic control to secure the requisite (3S,7S,8S)-configurations for the bielschowskysin synthesis. Unlike previously speculated, our results suggest that the most strained FBC-macrocycles bearing a E-(D7,8)-alkene moiety may stand as the true biosynthetic precursors to bielschowskysin and several other polycyclic natural products of this class.