Synthesis of 6,19-cyclopregnanes. Constrained analogues of steroid hormones.
A procedure for the synthesis of 6,19-cyclopregnanes is described involving an intramolecular alkylation reaction of Delta(4)-3-keto steroids with a 19-mesylate in the presence of KOH in isopropanol. Three 6,19-cyclopregnanes were prepared (4, 5 ,9); in the rat, 6,19-cycloprogesterone (4) and its 21-hydroxy derivative 5 displaced [3H]-dexamethasone from glucocorticoid receptors, the former compound being more active. Both compounds did not compete with [3H]-aldosterone for kidney mineralocorticoid receptors nor with [3H]-R5020 for uterus progesterone receptors.
Di Chenna
Pablo H
PH
Departamento de Química Orgánica and UMYMFOR (CONICET-FCEN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
Veleiro
Adriana S
AS
Sonego
Juan M
JM
Ceballos
Nora R
NR
Garland
M Teresa
MT
Baggio
Ricardo F
RF
Burton
Gerardo
G
D000818:Animals; D003500:Cyclization; D006728:Hormones / Q000138:chemical synthesis / Q000737:chemistry*; D007661:Ketoses / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011278:Pregnanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D006728:Hormones; D007661:Ketoses; D011278:Pregnanes; D011965:Receptors, Glucocorticoid; D013256:Steroids