Neighboring group participation. Part 15. Stereoselective synthesis of some steroidal tetrahydrooxazin-2-ones, as novel presumed inhibitors of human 5alpha-reductase.
During the alkaline methanolysis of 3beta-acetoxy-21-chloromethyl-pregn-5-ene-20beta-N-phenylurethane, and its p-substituted phenyl derivatives, cyclization occurs, in the course of which 17beta-[3-(N-phenyl)tetrahydrooxazin-2-on-6-yl]androst-5-en-3beta-ol and its p-substituted phenyl derivatives are formed. The cyclization takes place with (N(-)-6) neighboring group participation. Oppenauer oxidation of the 3beta-hydroxy-exo-heterocyclic steroids yielded the corresponding delta4-3-ketosteroids. The structures of the new compounds were proved by IR, 1H and 13C NMR spectroscopy, using up-to-date measuring techniques such as 2D-COSY, HMQC, and HMBC. The inhibitory effects (CI50) of the delta4-3-ketosteroids on 5alpha-reductase were studied.
Wölfling
János
J
Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720, Hungary.
Hackler
László
L
Mernyák
Erzsébet
E
Schneider
Gyula
G
Tóth
István
I
Szécsi
Mihály
M
Julesz
János
J
Sohár
Pál
P
Csámpai
Antal
A
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000737:chemistry; D058891:5-alpha Reductase Inhibitors; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D010078:Oxazines; D013256:Steroids; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase