合成路线: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).
合成路线: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.
合成路线: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.
参考文献标题:Novel spironolactones and process for their preparation
文献作者:Losert,W.; Bittler,D.; Vasals-Stenzel,J.; Wiechert,R.; Kerb,U.(Schering AG)
参考来源:DE 2652761; US 4129564
合成路线: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.
参考文献标题:Mespirenone
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1987,12(1),27
合成路线: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.
参考文献标题:Aldosterone antagonists.2.New 7alpha-(acetylthio)-15,16-methylene spirolactones
文献作者:Bittler,D.; Casals-Stenzel,J.; Wiechert,R.; Losert,W.; Laurent,H.; Schillinger,E.; Nishino,Y.; Nickisch,K.
参考来源:J Med Chem 1987,30(8),1403
产品链接: CAS No. 87952-98-5››