Structure, absolute configuration, and conformation of the antimalarial compound, Artemisinin

Abstract

The crystal and molecular structure of the antimalarial compound Artemisinin (formerly known as Qinghaosu), C₁₅H₂₂O₅ has been determined by direct methods. Crystals are orthorhombic colorless needles, space group P2₁2₁2₁, Z = 4. D _c = 1.299 g cm ⁻³, with unit cell parameters a = 6.3543(9), b = 9.439(3), c= 24.066(4) Å. The molecule incorporates a fused ring system containing a six-membered ring C which includes an oxygen bridge and a peroxy-bridge. The ring C has a distorted boat conformation and the C - O - O - C torsion angle is 47.8(2)°. Rings A and D have symmetrical chair and distorted chair conformations, repectively. Ring junctions A/B, A/D, and C/D are cis, junction B/D is trans. All inter-molecular contacts are van der Waals. The absolute configuration of Artemisinin was determined from the refined value of the Flack x parameter. [The atomic coordinates given in a previous structure analysis, “Crystal Structure and Absolute Configuration of Qinghaosu,” Qinghaosu Research Group, Institute of Biophysics, Academica Sinica, Scientia Sinica, Vol. XXIII No. 3, 380 (1980), do not display the molecule in its absolute configuration.]