title: Neighboring group participation Part 17 Stereoselective synthesis of some steroidal 2-oxazolidones, as novel potential inhibitors of 17alpha-hydroxylase-C(17,20)-lyase.
abstract: During the alkaline methanolysis of 3beta-acetoxy-21-chloropregn-5-ene-20beta-N-phenylurethane (4a), and its 4-monosubstituted (4b-e) and 3,5-disubstituted (4f) phenyl derivatives, cyclization occurs, in the course of which 17beta-[3-(N-phenyl)-2-oxazolidon-5-yl]androst-5-en-3beta-ol (5a) and its substituted phenyl derivatives (5b-f) are formed. The cyclization takes place with (N(-)-5) neighboring group participation. The reaction of 3beta-acetoxy-21-azidopregn-5-en-20beta-ol (3d) with triphenylphosphine gave 3beta-acetoxy-21-phosphiniminopregn-5-en-20beta-ol, which reacted in situ with carbon dioxide with the participation of the sterically favored 20beta-OH to give the unsubstituted steroidal cyclic carbamate (8). Oppenauer oxidation of the 3beta-hydroxy-exo-heterocyclic steroids (5a-f, 9) yielded the corresponding Delta(4)-3-ketosteroids (7a-f, 10). The inhibitory effects (IC(50)) of these compounds on rat testicular C(17,20)-lyase were investigated with an in vitro radioligand incubation technique. The N-unsubstituted 17beta-(2-oxazolidon-5-yl)-androst-4-en-3-one derivative (10) was found to be a potent inhibitor (IC(50)=3.0 microM).
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: Dóra
authors.initials: D
authors.lastname: Ondré
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Iványi
authors.forename: Gyula
authors.initials: G
authors.lastname: Schneider
authors.forename: István
authors.initials: I
authors.lastname: Tóth
authors.forename: Mihály
authors.initials: M
authors.lastname: Szécsi
authors.forename: János
authors.initials: J
authors.lastname: Julesz
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013260:Steroids, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013737:Testis / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D023303:Oxazolidinones; D013260:Steroids, Heterocyclic; D013254:Steroid 17-alpha-Hydroxylase