The acylation of spiro[pregnane-17,2'-tetrahydrofuran]-4,6,15-triene-3,5'-dione (I) with thioacetic acid in refluxing methanol gives the 7-acetylthio derivative (II), which is methylenated with trimethylsulfoxonium iodide and NaH in refluxing DMSO, yielding the 15beta,16beta-methylene derivative (III). Finally, this compound is dehydrogenated with 2,3-dichloro-5,6-dicyanobenzoquinone (IV) in refluxing benzene.
3beta-Hydroxy-5-androsten-17-one (XVII) is dihydroxylated microbiologically by means of Colletotrichum lini to 3beta,7alpha,15alpha-trihydroxy-5-androsten-17-one (XVIII), which is treated with acetone and boron trifluoride etherate yielding the acetonide (XIX). Hydrolysis of (XIX) with HCl in methanol affords the 3beta,7beta,15alpha-isomer (XX), which is also obtained from (XVIII) by isomerization with perchloric acid in methylisobutylketone. Selective acylation of (XX) with pivaloyl chloride affords the 3beta,15alpha-dipivaloyloxy compound (XXI), which is submitted to cyclopropanation with trimethylsulfoxonium iodide and NaOH as before yielding (IX).
3) Reaction of 3beta-hydroxy-15beta,16beta-methylene-5-androsten-17-one (I) with 1-bromo-3,3-dimethoxypropane (XIII) and lithium in THF gives the 17alpha-(3,3-dimethoxypropyl) derivative (XIV), which by treatment with 70% acetic acid provides the spiro compound (XV). Oxidation of compound (XV) with cyclohexanone in the presence of (i-PrO)3Al and then treatment with 2N H2SO4 affords 15beta,16beta-methylene-3-oxo-17alpha-pregn-4-ene-21,17-carbolactone (XVI). Treatment of (XVI) with chloranil in t-BuOH yields the pregnadiene carbolactone (XVII), which is finally reacted with trimethylsulfoxonium iodide (XVIII) and NaH in DMSO.
The condensation of 3,5-dihydroxy-15beta, 16beta-methyleneandrost-6-ene-17-one (I) with propargyl alcohol (II) by means of potassium ethoxide in THF gives 17alpha-(3-hydroxypropynyl)-15beta, 16beta-methyleneandrost-6-ene-3beta,5beta,17beta-triol (III), which is hydrogenated with H2 over RaNi in methanol yielding the 3-hydroxypropyl derivative (IV). The oxidation, with simultaneous cyclization and dehydration of (IV) with pyridine - CrO3, affords 15beta,16beta-methylene-3-oxo-17alpha-pregna-4,6-diene-21,17-carbolactone (V), which is treated with thioacetic acid in methanol - water to give the 7alpha-acetylthio derivative (VI). Finally, this compound is dehydrogenated with dicyano-dichloro-benzoquinone (DDQ) in refluxing benzene.