The Structure of 2,2-Dimethyl-3-ureido-6-phenoxyacetamidopenam* BY ZBIGNIEW DAUTER, MARIA BOGUCKA-LEDOCHOWSKA AND EDWARD BOROWSKI

Abstract

C16H20N404 S, M r = 364.43, an active derivative, resistant to penicillinase, with a ureide moiety instead of a carboxy group, crystallizes in the orthorhombic space group P212121 with a = 17.751 (6), b = 15.306 (4), e = * { 3,3-Dimethyi7-oxo-6-[ (phenoxyacetyl)amino l-4-thia1azabicyclo[ 3.2.0]hept-2-yl }urea. 0567-7408/81 / 122179-05501.00 6.493 (2) A, V = 1764 A 3, Z = 4, D m = 1.364, D c = 1.371 Mg m -3, F(000) = 768. R = 0.040 for 1704 observed independent reflections. The thiazolidine ring exhibits an envelope conformation with C(3) 0.52 A out of the plane through the remaining four atoms. The fl-lactam ring is folded 9 ° from planarity. Each molecule is hydrogen bonded to four neighbouring molecules. The resistance to fl-lactamase is caused by the changed chemical properties of the compound rather than by shielding of the fl-lactam. © 1981 International Union of Crystallography 2180 THE STRUCTURE OF 2,2-DIMETHYL-3-UREIDO-6-PHENOXYACETAMIDOPENAM Introduction Structure determination and refinement One of the crucial problems in the chemical modifications of penicillin is the development of compounds with increased resistance to penicillinases. The problem has been partially solved by the introduction of voluminous substituents into the acyl moiety of penicillin. The steric hindrance shields the fl-lactam from the attack of the enzyme and results in the high resistance of compounds like cloxacillin to the degradative action of penicillinase. Nevertheless compounds of that type exhibit activity only against Gram-positive bacteria. Extensive work has been done to develop other types of modified penicillins which, apart from not being the substrates of penicillinases, would exhibit activity against Gram-negative bacteria. A novel type of active penicillin derivative, namely the ureido analogues in which the carboxyl has been replaced by an unsubstituted or substituted ureido group, has been recently developed (Domaradzki, Mikotajczyk, Kazimierczak, Rogowska & Sikora, 1977). These compounds exhibit high resistance to penicillinase, although they do not contain an acyl moiety like normal penicillin G. The question arises whether the resistance to penicillinase of this type of compound is due to steric hindrance caused by the particular conformation of ureido analogues, or to the changed chemical properties of the compound and thus the changed susceptibility to enzyme action. Our studies were aimed at the elucidation of this problem.

6 Figures and Tables

Cite this paper

@inproceedings{Nelson2001TheSO, title={The Structure of 2,2-Dimethyl-3-ureido-6-phenoxyacetamidopenam* BY ZBIGNIEW DAUTER, MARIA BOGUCKA-LEDOCHOWSKA AND EDWARD BOROWSKI}, author={Maria Nelson}, year={2001} }