Theoretical Evidence for a Concerted Mechanism of the Oxirane Cleavage and A-Ring Formation in Oxidosqualene Cyclization

Formation of the B Ring in Steroids and Hopanoids from Squalene

“…Previous ab initio studies indicate that these ring closures are likely to proceed without the intervention of reactive intermediates. [2,3] Similar studies (density functional theory) have also been reported on the closure of rings A, [4] C, [5] and D. [6] Herein a detailed theoretical conformational study [7Ϫ11] of the model system 1 in its ring closure to 2 is reported, the results of which can account for these two stereochemically different pathways in the biosynthesis of steroids and hopanoids.…”

Enzyme Mechanisms for Triterpene Cyclization: New Pieces of the Puzzle

“…[9] For OSC, temporal overlap between the initial protonation step and A-and potentially B-ring cyclization has been inferred from nonenzymatic data and substrate-analogue studies and is sup- www.angewandte.org ported by computational results. [12][13][14] Computational studies have suggested an analogous mechanism for SHC. [15] The SHC complex with the substrate mimic 2-azasqualene shows a conformation in which the first four isoprene units orient themselves in a way such that only small displacements are required for the formation of a 6-6-6-or 6-6-5-tricycle ( Figure 1).…”

Enzyme Mechanisms for Polycyclic Triterpene Formation

“…Evidence for concerted epoxide opening and A-ring closure catalyzed by oxidosqualene ± lanosterol cyclases. [12,24] [10] Since the conformers of 14 and 15 which correspond to the optimal geometry for cation ± p-olefin cyclization constitute only a minor fraction of the rotamers of 14 and 15 which are present in solution, there would presumably be even greater anchimeric acceleration for the cyclization of the optimally prefolded conformers.…”