Synthesis of 6-azaprogesterone and 19-hydroxy-6-azasteroids

19-Hydroxy-6-azapregnanes were obtained from pregnenolone via a 7-azido-5-oxo-6-nor-5,7-secopregnane intermediate. The 6-azapregnane core was built in good yield in a straightforward way from the secosteroid, by means of a Staudinger (aza-Wittig) reaction. Finally the 19-hydroxy-6-azapregnane was transformed into 19-hydroxy-6-azaprogesterone (that cyclized spontaneously to the 19 → 3 hemiketal) and 6-azaprogesterone. The 6-azapregnanes lacked agonistic/antagonistic activity on the progesterone receptor.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The 6-azapregnane core may be obtained by a direct route via a Staudinger reaction. ► We synthesized 19-hydroxy-6-azaprogesterone (19 → 3 hemiketal) and 6-azaprogesterone. ► The 6-aza moiety causes the loss of affinity for the progesterone receptor.