Abstract

Background: Several steroid derivatives have been prepared using different protocols. The aim of study involved the synthesis of a diazepin-steroid derivative using androsterone as chemical tool.

Methods: Diazepin-steroid derivative was prepared by a series of reactions that involve; 1) Protection of the hydroxyl group from androsterone with tert-Butyldimethylsilyl chloride to form (3R,10S,13S)-3-((tert-butyldimethylsilyl)oxy)- 10,13-dimethylhexadecahydro-17H-cyclopenta[a]phenanthren-17-one (3-TBDS-androst-17-one); 2) catalytic α-hydroxylation of 3-TBDS-androst-17-one for preparation of 3-TBDS-16-hydroxy-steroid-17-one; 3) Reaction of 3-TBDS-16- hydroxy-steroid-17-one with p-nitrobenzoyl azide to form 3-TBS-17-oxo-steroid-triazadienium; 4) synthesis of a triazolsteroid derivative by reaction of 3-OTBS-17-oxo-steroid-triazadienium with 1-hexyne; 5) Removal of tert-Butyldimethyl- silanyloxy of the triazol-steroid derivative with hydrofluoric acid to form 16-triazole-3-hydroxy-steroid-17-one; 6) Reaction of 16-triazole-3-hydroxy-steroid-17-one with dimethyl sulfoxide to form the 16-triazole-steroid-3- carbaldehyde derivative; 7) synthesis of a enone-steroid derivative by the reaction of 16-triazole-steroid-3-carbaldehyde with acetophenone; 8) Reaction of ethylenediamine with the enone-steroid derivative for synthesis of a diazepin-steroid derivative. The structure of all compounds obtained was confirmed by spectroscopic and spectrometric methods.

Results: The ¹H NMR spectrum of diazepin-steroid shows signals at 0.85 and 1.06 ppm for methyl groups bound to steroid nucleus; at 0.90 for methyl group of arm bound to triazole ring; at 0.93-1.04, 1.14-1.36, 1.44-1.74, 1.90, 2.30, 2.60- 2.80 and 5.40 ppm for steroid moiety; at, 1.40, 1.80 and 2.44 ppm for methylene groups of arm bound to triazole ring; at 3.10, 3.12, 3.60 and 3.82 ppm for methylene bound to both amino and imino groups; at 3.22-3.56, 3.66 and 4.80 ppm for diazepine ring; 3.10, 3.12, 3.60 and 3.82 ppm for methylene groups bound to both amino and imino groups; at 5.60 ppm for amino groups; at 6.84 ppm for triazole ring; at 6.62-6.80 and 7.34-7.90 ppm for phenyl groups. The ¹³C NMR spectra displays chemical shifts at 14.30 ppm for methyl group of arm bound to triazole ring; at 11.66 and 16.30 ppm for methyl groups bound to steroid nucleus; at 20.62, 27.60-36.70, 41.20, 42.58, 46.70-48.88, 54.32 and 55.00 and 82.00 ppm for steroid moiety; at 24.18-27.16 ppm for methylene groups of arm bound to triazole ring; at 115.70, 142.60 ppm for triazole ring; at 41.00, 41.32, 54.46, 57.77 and 163.18-165.30 ppm for methylene groups bound to both amino and imino groups; at 44.38, 53.00 and 95.60 ppm for diazepine ring; at 116-138.30 and 154.40 ppm for phenyl groups; at 148.50 and 172.62 ppm for imino groups. In addition, the presence of compound diazepin-steroid was confirmed with mass spectrum which showed a molecular ion at m/z 773.54.

Conclusions: In this study is reported a straightforward route for synthesis of a Diazepin-steroid derivative using some strategies. The proposed methods offer some advantages such as simple procedure and ease of workup.

Keywords: Androsterone, diazepin, steroid, synthesis.

Graphical Abstract