Reactions of the four diastereomeric 16-amino-17-hydroxy-3-methoxy-estra-1,3,5(10)-trienes with aromatic ortho-hydroxy and heteroaromatic α-aldehydes and with 1,3-dicarbonyl compounds—molecular structures of condensation products and of copper(II) complexes

• Published in: Steroids 2000-06, Vol.65 (6), p.305-318
• Main Authors: Dubs, Manuela, Krieg, Reimar, Görls, Helmar, Schönecker, Bruno
• Format: Article
• Language: English
• Subjects: Aldehydes - chemistry; Alicyclic compounds, terpenoids, prostaglandins, steroids; Amino alcohol derivatives; Amino Alcohols - chemistry; Chemistry; Condensed matter: structure, mechanical and thermal properties; Copper - chemistry; Copper complexes; Exact sciences and technology; Hydrogen Bonding; Inorganic compounds; Ligands; Magnetic Resonance Spectroscopy; Metal complexes; Molecular Structure; Organic chemistry; Physics; Preparations and properties; Schiff bases; Steroids; Structure of solids and liquids; crystallography; Structure of specific crystalline solids; X-ray analysis; X-Ray Diffraction
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/S0039-128X(00)00092-1

Vicinal amino alcohols of steroids have been used as starting materials for the synthesis of chiral ligands with defined arrangements of functional groups. Condensation of the four diastereomeric 16,17-steroid amino alcohols 1a– 1d with aromatic o-hydroxy and heteroaromatic α-aldehydes afforded the Schiff bases 2–6. When the 16,17-substituted compounds 2d, 5d, 6a, and 6d were in solution, the isomeric oxazolidines were detectable by 1H NMR spectroscopy. The formation of oxazolidines could be avoided by using bulky aldehydes. Reduction of the Schiff bases (also in mixtures with oxazolidines) with NaBH 4 yielded the new N-substituted amino alcohols 12–15. The condensation products of 1a– 1d with 1,3-dicarbonyl compounds ( 7 and 8) exhibited the 1-enamino-3-oxo structure ( 1H NMR spectroscopy). By means of X-ray analysis of 2a– 2d, 3d, 7a, and 7c, the torsion angles for the 16N, 17O substituents, which are important for a participation of the 17O substituent in the complexation of metal ions, have been determined. Furthermore, a preferred arrangement between the chelate ring and the steroid plane existed in all investigated condensation products attributable to torsion angles 16H-C16–16N-C of 5–61°. This arrangement was also preserved in the copper(II) complex 11 with 16α,17β- trans configuration of the bidentate steroid ligand and a ratio of 2:1 for ligand: copper in contrast with dimeric copper(II) complexes with a tridentate steroid ligand of 16β,17β- cis configuration (ratio of 1:1 for ligand:copper). The crystal structures of the condensation products are also discussed. In most cases, intermolecular hydrogen bonds between 17-hydroxy groups and the chelate oxygen caused polymeric strands.