The first enantioselective total synthesis of the hexacyclopropane natural product U-106305, which is produced by Streptomyces sp. UC 11136, is described in full detail. Considerations on the biosynthesis of U-106305 and its close resemblance to the pentacyclopropane bacterial metabolite FR-900848 (10) led to the proposal that its previously unknown stereostructure should be represented as 11. The central C-2-symmetrical quinquecyclopropane unit of 11 was assembled by repeatedly using a three-step cyclopropane ''homologation'' sequence in an efficient bidirectional approach, Desymmetrized quinquecyclopropane 23 was converted to dienol 13 which was monocyclopropanated stereo-and regioselectively to provide hexacyclopropane 25. Deoxygenation was achieved by conversion to thioether 29 and desulfurization, The synthesis was completed by a one-pot deprotection-oxidation-Wittig olefination sequence to give 11. The synthetically derived material was found to be identical in all respects to an authentic sample of U-106305 thus establishing the stereochemical identity of this natural product for the first time. In the course of our studies, several oligocyclopropane derivatives were found to be crystalline compounds and their structures were determined by X-ray crystallography. Among others, X-ray structures of two diastereomeric heptecyclopropanes 27 and 28 are presented, The synthesis of five analogs of U-106305 including the structural hybrid with FR-900848 (Lsa) are described, An approach to FR-900848 (10) using a late desymmetrization of a C-2-symmetrical quatercyclopropane tetraene 52 is outlined.