Sesquiterpenoids. Part 26. X-Ray crystallographic analysis of mikanokryptin, a cytotoxic guaianolide

Abstract

The stereochemistry of mikanokryptin, a cytotoxic guaianolide, has been defined by X-ray diffraction. In the α-methylene γ-lactone the CC–CO and C_α–C_β–C_γ–O torsion angles, 6 and 26°, are paired in sign. Whereas molecular mechanics calculations for a series of chair and twist chair conformers indicate that the most stable form of an isolated methylenecycloheptane is a twist chair in which an approximate C₂ axis of the ring passes through the carbon atom adjacent to that bearing the exocyclic methylene group, the methylenecycloheptane ring in the sesquiterpenoid has a conformation of the chair type and the difference is related to constraints imposed by the cyclopentenone and lactone ring fusions. Crystals of mikanokryptin are orthorhombic, space group P2₁2₁2₁, with a= 10.366, b= 9.479, c= 13.329 Å, and Z= 4. The crystal structure was elucidated by direct phasing methods and the atomic parameters were subsequently adjusted by least-squares calculations which converged at R 4.3% over 2 277 diffractometer |F₀| values.