title: Synthesis of 21-nitrogen substituted pregna-5,17(20)-dienes from pregnenolone.
abstract: The facile synthesis of six [17(20)Z]- and [17(20)E]-isomeric 3β-hydroxy-pregna-5,17(20)-dien-21-oyl amides and three [17(20)E]-3β-hydroxy-2-[prergna-5,17(20)-dien-20-yl]-oxazolines from pregnenolone is presented. The synthetic scheme consists of transformation of pregnenolone into the known 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one followed by reaction with ethanolamine, 2-methyl-2-aminopropanol, and (1-aminocyclohexyl)methanol resulted in mixture of [17(20)E]- and [17(20)Z]-pregna-5,17(20)-dien-21-(2-hydroxy)-oyl amides; separation of [17(20)E]- and [17(20)Z]-isomers; their cyclization into [17(20)E]-oxazolines under action of POCl(3) in pyridine, and removal of acetate protecting groups. Significantly different orientation of nitrogen containing substituents in [17(20)Z]- and [17(20)E]-isomers regarding to steroid backbone enables their configuration to be easily identified by NMR spectroscopy. All synthesized compounds did not exhibit marked toxic effects in three cell lines (MCF-7, Hep G2, and LNCaP). In androgen-sensitive LNCaP cells all testing compounds at concentrations of 50 nM potently stimulated proliferation.
authors: VN Orekhovich Institute of Biomedical Chemistry, RAMS, Moscow, Russia.
authors: Sergey V
authors: SV
authors: Stulov
authors: Yaroslav V
authors: YV
authors: Tkachev
authors: Roman A
authors: RA
authors: Novikov
authors: Maria G
authors: MG
authors: Zavialova
authors: Vladimir P
authors: VP
authors: Timofeev
authors: Alexander Yu
authors: AY
authors: Misharin
mesh_terms: D000577:Amides / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003500:Cyclization; D019856:Ethanolamine / Q000737:chemistry; D006801:Humans; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010080:Oxazoles / Q000737:chemistry; D011245:Pregnadienes / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D011284:Pregnenolone / Q000737:chemistry*; D011412:Propanolamines / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry
chemical_list: D000577:Amides; D010080:Oxazoles; D011245:Pregnadienes; D011412:Propanolamines; D011725:Pyridines; D019856:Ethanolamine; D011284:Pregnenolone; C034448:2-aminopropanol; C023666:pyridine