A SYNTHESIS OF 11-HOMO-ALDOSTERONE

Article abstract of DOI:10.1016/0040-4020(82)85028-X

A synthesis of 11-homo-aldosterone acetate (1a) is described. 3β-Acetoxy-11-methylene-5α,25D-spirostan (3) was converted in 4 steps into 3β-acetoxy-11β-acetoxymethyl-5α-pregnan-20-one (9, Chart I), which was photocyclized to 20a, saponified regioselectively, and oxidized to 3-oxo-11β-acetoxymethyl-18,20-cyclopregnan-20α-ol-3-one (22, Chart II).Introduction of the 1,4-diene in 22 followed by a selective reduction of the 1-ene afforded 11β-acetoxymethyl-18,20-cyclopregn-4-en-20α-ol-3-one (26).Finally, the 18,20-cyclo ring of 26 was manipulated through 30, 31, 32, 33 to produce 1a.The bulky 11β-acetoxymethyl group distorted the steroid molecule to such an extent that the routine photochemical functionalization of the angular Me-18 via a nitrite or a hypoiodite became inoperative and routine procedures for introduction of a 4-ene into 5α-3-one via a 1,4-dien-3-one were unsuccessful.Two new methods for the introduction of a 4-ene into steroidal 5α-3-ones were investigated using 5α-cholestanone and 5α-dihydrotestosterone as models.The first route, which was applicable to the synthesis of 1a, was the stepwise introduction of a 1-ene and a 4-ene utilizing Sharpless's acidic phenylselenyl chloride procedure, followed by a selective reduction of the 1-ene.The second route, which appeared equally promising, was protection of the C-2 site with N-methylanilinomethylene followed by introduction of the 4-ene and subsequent deprotection of the C-2.