Design and synthesis of new dioxa diazaspiro[bicyclo [9.4.2] heptadecane-steroid-dienyne derivative from estrone and OTBS-estrone

Several bicycle-derivatives have been prepared using different protocols; nevertheless, expensive reagents and special conditions are required. The aim of this study was synthesize a dioxa-diazaspiro[bicyclo[9.4.2]heptadecane-steroid-dienyne derivative by a series of reactions which involving; a) alkinilization of estrone or OTBS-estrone with 5-hexyn-1-ol to form two propargyl alcohol derivatives (3 or 4); b) esterification 3 or 4 with succinic acid to form two dioxaspiro-steroid-cyclotridecan derivatives (5 or 6); c) preparation of diazaspiro[bicycle[9.4.2]heptadecane-steroid-4 amino complex (7 or 8) by reaction of 5 or 6 with ethylenediamine; d) removal of silyl fragment of 8 via hydrofluoric acid to form the compound diazaspiro[bicycle[9.4.2] heptadecane-steroid-3′-ol (9); e) preparation of diazaspiro[bicycle[9.4.2]heptadecane-steroid-4-oxobutanoic acid (10) via esterification of 9 with succinic acid; f) amidation of 10 with ethylenediamine to form diazaspiro[bicyclo[9.4.2] heptadecane-steroid-4-aminobutanoate (11); g) synthesis of dioxadiazaspiro [bicyclo[9.4.2] heptadecane-steroid-dienyne (12) via pyrrolization of 11 using boric acid. The chemical structure of compounds was confirmed by NMR spectroscopic data.