锦州古塔能进去吗:孕二烯酮 [CAS:60282-87-3]合成路线图解??有机化学网

药物详细合成路线

Chemical Name： 13-Ethyl-17-hydroxy-18,19-dinor-17alpha-pregna-4,15-dien-20-yn-3-one Generic Name： 孕二烯酮;Gestodene Other Names： Gestodene;SH-546;SHB-331 CAS： 60282-87-3 Formula： C₂₁H₂₆O₂ Mole Weight： 310.44017 structure： Company： Schering AG (Originator) Usage： Bone Diseases, Treatment of, ENDOCRINE DRUGS, Gynecological Disorders, Treatment of , Hormone Replacement Therapy, METABOLIC DRUGS, Prevention of Osteoporosis, Progestogens Route 1 18-Methyl-4-oestrene-3,17-dione (I) is hydroxylated by fermentation with Penicillium raistrickii giving the 15alpha-hydroxy compound (II), which is ketalized with 2,2-dimethylpropanediol (A), triethyl orthoformate and p-toluenesulfonic acid in CH2Cl2 giving a mixture of the DELTA(5-6) and DELTA(5-10)-ketals (IIIa-b). These ketals are mesylated witn methanesulfonyl chloride in pyridine yielding the mesyl ester (IVa-b), which is treated with sodium acetate in DMF to afford the oestradiene ketal (Va-b). Finally, this compound is treated with ethynylmagnesium bromide (B) and refluxed with oxalic acid (C) in methanol. Intermediates: Serial No. L-glutamine (A) 18-(4-iodophenyl)-1-octadecanol (C) 3-(3-iodopropyl)phenyl phenyl ether; 1-(3-iodopropyl)-3-phenoxybenzene (B) N,N-diethyl-1-ethanamine; N,N,N-triethylamine; triethylamine (I) methyl 7-[(3R)-3-hydroxy-5-oxo-1-cyclopenten-1-yl]heptanoate (II) methyl 7-((3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-oxo-1-cyclopenten-1-yl)heptanoate (IIIa) methyl 7-((1R,2R,3R)-2-(3-butenyl)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-oxocyclopentyl)heptanoate (IIIb) methyl 7-((1R,2R,3R,5S)-2-(3-butenyl)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxycyclopentyl)heptanoate (IVa) methyl 7-((1R,2R,3R,5S)-2-(3-butenyl)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclopentyl)heptanoate (IVb) methyl 7-[(1R,2R,3R,5S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-(3-oxopropyl)cyclopentyl]heptanoate (Va) 1-benzothiophen-2-yllithium (Vb) Reference 1:     Hofmeister, H.; Wiechert, R.; Annen, K.; Laurent, H.; Steinbeck, H.; Steroids and pharmaceutical compositions thereof. BE 0847090; FR 2326927; GB 1569135; JP 52046060; US 4081537 . Reference 2:     Castaner, J.; Blancafort, P.; Gestodene. Drugs Fut 1977, 2, 12, 805.
Route 2 Ketals (IIIa-b) can also be treated with trimethylsilyl chloride in pyridine to give the trimethylsilyl derivative (VIa-b), which is then treated with ethynylmagnesium bromide (B) and oxalic acid (C) in methanol. Intermediates: Serial No. 18-(4-iodophenyl)-1-octadecanol (C) 3-(3-iodopropyl)phenyl phenyl ether; 1-(3-iodopropyl)-3-phenoxybenzene (B) methyl 7-((3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-oxo-1-cyclopenten-1-yl)heptanoate (IIIa) methyl 7-((1R,2R,3R)-2-(3-butenyl)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-oxocyclopentyl)heptanoate (IIIb) methyl 7-((1R,2R,3R,5S)-2-[3-(1-benzothiophen-2-yl)-3-hydroxypropyl]-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclopentyl)heptanoate (VIa) methyl 7-[(1R,2R,3R,5S)-2-[3-(1-benzothiophen-2-yl)-3-hydroxypropyl]-3,5-dihydroxycyclopentyl]heptanoate (VIb) Reference 1:     Hofmeister, H.; Wiechert, R.; Annen, K.; Laurent, H.; Steinbeck, H.; Steroids and pharmaceutical compositions thereof. BE 0847090; FR 2326927; GB 1569135; JP 52046060; US 4081537 . Reference 2:     Castaner, J.; Blancafort, P.; Gestodene. Drugs Fut 1977, 2, 12, 805.
Route 3 Ketals (IIIa-b) can also be acetylated with acetic anhydride in pyridine to the acetate (VIIa-b), which is then treated with ethynylmagnesium bromide (B) and oxalic acid (C) in methanol. Intermediates: Serial No. 18-(4-iodophenyl)-1-octadecanol (C) 3-(3-iodopropyl)phenyl phenyl ether; 1-(3-iodopropyl)-3-phenoxybenzene (B) methyl 7-((3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-oxo-1-cyclopenten-1-yl)heptanoate (IIIa) methyl 7-((1R,2R,3R)-2-(3-butenyl)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-oxocyclopentyl)heptanoate (IIIb) 2-([(4-methylphenyl)sulfonyl][2-[[(4-methylphenyl)sulfonyl](2-[[(4-methylphenyl)sulfonyl]oxy]ethyl)amino]ethyl]amino)ethyl 4-methylbenzenesulfonate (VIIa) 4-methyl-N-[2-[[(4-methylphenyl)sulfonyl](2-[[(4-methylphenyl)sulfonyl]amino]ethyl)amino]ethyl]benzenesulfonamide (VIIb) Reference 1:     Hofmeister, H.; Wiechert, R.; Annen, K.; Laurent, H.; Steinbeck, H.; Steroids and pharmaceutical compositions thereof. BE 0847090; FR 2326927; GB 1569135; JP 52046060; US 4081537 . Reference 2:     Castaner, J.; Blancafort, P.; Gestodene. Drugs Fut 1977, 2, 12, 805.