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 Cα–Cβ–Cγ–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 A, 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.