TY - JOUR
T1 - Synthesis of 19-noraldosterone, a potent mineralocorticoid
AU - Harnik, M.
AU - Kashman, Y.
AU - Cojocaru, M.
AU - Rosenthal, T.
AU - Morris, D. J.
PY - 1986/6
Y1 - 1986/6
N2 - 19-Noraldosterone has been prepared for biological re-evaluation through an extension of a recent synthesis of 19-hydroxyaldosterone: 21-hydroxy-6β,19-epoxy-4-pregnene-3,20-dion-20-ethylene ketal-18,11β-lactone (1a) was acetylated and then reduced with zinc-acetic acid-isopropanol to the 19-o1 2b. Treatment with sodium acetate transposed the double bond into conjugation, and 2a thus obtained was oxidized with pyridinium chlorochromate to the 19-oxo compound 3. Decarbonylation to the 19-nor lactone 4 was effected by heating with alkali. Protection of the C-3 carbonyl was achieved by ketalization and the resulting mixture of the 5-ene and 5(10)-ene ketals 5 was reduced with DIBAH to the corresponding mixture of the hemiacetals 6. Acid hydrolysis of the latter afforded 19-noraldosterone (7), accompanied by the 18,21-anhydro ketal 8. 19-Noraldosterone in the solid state exists in the cyclic form 7b, which appears to be also the predominant isomer present under conditions of mass spectrometry. [1H]NMR indicates that in chloroform 19-noraldosterone exists mostly as an equilibrium mixture of structures 7a and 7b. Sodium periodate oxidation furnished the γ-etiolactone 9, confirming the 17β configuration in 7.
AB - 19-Noraldosterone has been prepared for biological re-evaluation through an extension of a recent synthesis of 19-hydroxyaldosterone: 21-hydroxy-6β,19-epoxy-4-pregnene-3,20-dion-20-ethylene ketal-18,11β-lactone (1a) was acetylated and then reduced with zinc-acetic acid-isopropanol to the 19-o1 2b. Treatment with sodium acetate transposed the double bond into conjugation, and 2a thus obtained was oxidized with pyridinium chlorochromate to the 19-oxo compound 3. Decarbonylation to the 19-nor lactone 4 was effected by heating with alkali. Protection of the C-3 carbonyl was achieved by ketalization and the resulting mixture of the 5-ene and 5(10)-ene ketals 5 was reduced with DIBAH to the corresponding mixture of the hemiacetals 6. Acid hydrolysis of the latter afforded 19-noraldosterone (7), accompanied by the 18,21-anhydro ketal 8. 19-Noraldosterone in the solid state exists in the cyclic form 7b, which appears to be also the predominant isomer present under conditions of mass spectrometry. [1H]NMR indicates that in chloroform 19-noraldosterone exists mostly as an equilibrium mixture of structures 7a and 7b. Sodium periodate oxidation furnished the γ-etiolactone 9, confirming the 17β configuration in 7.
UR - http://www.scopus.com/inward/record.url?scp=0022480657&partnerID=8YFLogxK
U2 - 10.1016/0022-4731(86)90378-X
DO - 10.1016/0022-4731(86)90378-X
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AN - SCOPUS:0022480657
SN - 0022-4731
VL - 24
SP - 1163
EP - 1169
JO - Journal of Steroid Biochemistry
JF - Journal of Steroid Biochemistry
IS - 6
ER -