X-Ray-Diffraction Study and Determination of Absolute Configuration of the Anticancer Drug S(–) Cyclophosphamide (Endoxan, Cytoxan, NSC-26271)
Ryszard W. Adamiak, Wolfram Saenger, Ryszard W Kinas, Wojciech J. Stec · Zeitschrift für Naturforschung C · 1977
(--)Cyclophosphamide(1) crystallized from tetrachloromethane in the triclinic space group P1 with cell dimensions a = 10.500 (4) A, b = 10.490 (4) A, c = 10.761 (4) A, alpha = 110.0 (2) degrees, beta = 110.0 (2) degrees, gamma = 108.9 (2) degrees. Three molecules are contained in the unit cell. The X-ray analysis was based on diffractometer measurement of 2635 independent reflections and the structure was solved by Patterson and direct methods. The final R and Rw factors after full-matrix least-squares refinement are 0.0717 and 0.0677, respectively. The absolute configuration is S based on Hamilton's R-factor ratio test. The oxazaphosphorinane ring exists in a chair form with the bis-beta chloroethyl-amino group in equatorial position and about perpendicular to and bisecting the O--P--N plane. The structure is similar to that found in racemic 1 except a different conformation about one ethyl-amino N--C bond.