Regioselective reactions of 1,2-dehydroprogesterone: syntheses of pregnane derivatives as possible contragestational agents.
A few pregnane derivatives were synthesized from 1,2-dehydroprogesterone (1). Ring A of 1,2-dehydroprogesterone was aromatized without affecting C-20, and the resulting acetoxy compound (2) after hydrolysis yielded 1-hydroxy-4-methyl-19-norpregna-1,3,5(10)-trien-20-one (3). Reactions of the phenol (3) with alkyl halides yielded the ethers 6a-6b and 7. Opening of the oxirane ring in 7 with secondary amines furnished the aminoalcohols 8a-8b. Friedelcraft's reaction of 3 with maleic anhydride and chloracetyl chloride led to the formation of 9 and 10, respectively. Base-catalyzed ring closure of 10 yielded 1-acetyl-12a-methyl-8-oxo-5[H]-1,2,3,3a,3b,4,8,9,10b,11,12, 12a-dodecahydrocyclopenta (7,8)-phenanthro (3,4-b) furan (11), which reacted with aromatic aldehydes regioselectively to furnish 12a-12b. Reaction of 1 with triethylorthoformate in the presence of boron trifluoride etherate involved the participation of C-21, and the carbonyl at C-3 remained unaffected. The product 13 was identified as 21-[2-hydroxyvinyl]-21-norpregna-1,4-diene-3,20-dione. Reductive amination with sodium cyanoborohydride in the presence of ammonium acetate did not attack ring A and smoothly furnished the amine 14 which, on reaction with succinic anhydride, gave 20-succinamylpregna-1,4-dien-3-one (15).
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Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India.
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Bhaduri
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AP
D055598:Chemical Phenomena; D002621:Chemistry; D003271:Contraceptive Agents, Female / Q000138:chemical synthesis*; D004951:Esterification; D008299:Maleic Anhydrides; D015394:Molecular Structure; D011245:Pregnadienes / Q000138:chemical synthesis / Q000737:chemistry; D011278:Pregnanes / Q000138:chemical synthesis*; D011374:Progesterone / Q000031:analogs & derivatives* / Q000737:chemistry
D003271:Contraceptive Agents, Female; D008299:Maleic Anhydrides; D011245:Pregnadienes; D011278:Pregnanes; C070235:20-succinamylpregna-1,4-dien-3-one; C038897:1-dehydroprogesterone; D011374:Progesterone