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A new method has been developed,for the construction of the side chain of Cl , sterols from Czl-20-keto steroids and used for the synthesis of A16-and cis-A1~~*O~-cholesterol. The a,p-unsaturated nitrile 1, obtained by the dehydration of the cyanohydrin of pregnenolone acetate, was treated with isoamylmagnesium bromide to give the @,@-unsaturated ketone 3, which was isomerized to the p, y-unsaturated ketone 6 by treatment with base. The 22-keto group of 3 and 6 was then converted into the 22-methlene group by treatment of their 22-ethylene thioketal derivatives with lithium and ethylamine to give C~S -A~~( *~) -and Al6-cho1esterol, respectively. Alternatively, the enone 3 was converted into an allyl ether 22, which was then treated with lithium and ethylamine to give ~is-A~~(~o)-cholesterol. The 17-20 double bond of 3 and the 16-17 double bond of 6 has been selectively reduced to give 22-ketocholesterol, which was then converted into cholesterol via its 22-ethylene thioketal.

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Several derivatives of the highly active aldosterone antagonists dihydrospirorenone (2) and spirorenone (3) were synthesized. The purpose of these efforts was to prepare compounds exhibiting reduced endocrinological properties with the same or better aldosterone antagonistic activity than that of spirorenone. The 1 alpha,2 alpha-methylene derivative 20 has a similar aldosterone antagonistic potency compared to that of spirorenone but does not show decreased endocrinological side effects. Other substituents as in compounds 4-11, 15-19, and 21 sharply decreased the aldosterone antagonistic activity of 2 or 3, respectively.