Stereoselective synthesis of spiro and condensed pyrazolines of steroidal α,β-unsaturated ketones and nitrilimines by 1,3-dipolar cycloaddition

• Published in: Steroids Vol. 74; no. 6; pp. 520 - 525
• Main Authors: Mernyák, Erzsébet, Kozma, Eszter, Hetényi, Anasztázia, Márk, László, Schneider, Gyula, Wölfling, János
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 01.06.2009; Elsevier
• Subjects: Biochemistry & Molecular Biology; Biological and medical sciences; C 70 fullerenes; Cyclization; Cycloadditions; Endocrinology & Metabolism; Fundamental and applied biological sciences. Psychology; Imines - chemistry; Ketones - chemical synthesis; Ketones - chemistry; Life Sciences & Biomedicine; MALDI; Models, Chemical; Models, Molecular; Molecular Structure; Nitriles - chemistry; Nitrilimines; Pyrazoles - chemistry; Pyrazolines; Science & Technology; Stereoisomerism; Steroids - chemical synthesis; Steroids - chemistry; Vertebrates: endocrinology; Nitrilimines; Cycloadditions; Pyrazolines; MALDI; C 70 fullerenes; ASSISTED LASER DESORPTION/IONISATION; SERIES; INHIBITORS; ESTRONE; DERIVATIVES; C-70 fullerenes; MASS-SPECTROMETRY; Biosynthesis; C70 fullerenes
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2009.02.001

Effective syntheses of endo- and exocyclic α,β-unsaturated ketones as C C dipolarophiles were carried out in the 13α-estrone series. The 1,3-dipolar cycloadditions of 15,16α,β-unsaturated ketones of 13α-estrone 3-methyl and 3-benzyl ether with nitrilimines stereoselectively furnished two regioisomers of new condensed pyrazolines in a ratio of 2:1. The main product was the isomer obtained by the attack of the N-terminus of the 1,3-dipole on the carbon atom β to the carbonyl group of the dipolarophile. The nitrilimine cycloadditions to the 16-methylene-17-ketones of 13α-estrone 3-methyl and 3-benzyl ether stereo- and regioselectively furnished spiropyrazolines. The attack of the N-terminus of the dipole occurred on the α-carbon of the α,β-unsaturated ketones. The reactions were performed under both homogeneous and heterogeneous conditions. Silver acetate as a base proved more effective than its triethylamine counterpart. Changes in regio- and stereoselectivities were not observed on variation of the conditions of the cycloaddition reactions. The structures of the new products were determined by NMR (one- and two-dimensional) and MALDI TOF MS techniques, with C 70 fullerenes as matrix in the latter case.