Neurosteroids: 7-aza-allopregnanolone—a poor substitute for allopregnanolone

7-Nor-20-oxopregn-5-en-3β-yl acetate was converted into (20 R)-5β,6β-epoxy-7-nor-5β-pregnane-3β,20-diyl diacetate in three steps. Stereospecific migration of the 6α-hydride ion led to a 6-oxo derivative with a 5α-configuration. The ( Z)-oxime of this ketone underwent Beckmann rearrangement to yield a lactam with the nitrogen in position 7. Lithium aluminium hydride reduction yielded the dihydroxy amine, which was either oxidised or Boc-protected and then oxidised to 7-aza-5α-pregnane-3,20-dione. Its regioselective reduction produced 7-aza-3α-hydroxy-5α-pregnan-20-one—a poor inhibitor for the binding of [ 35 S]TBPS to the GABA A receptor. The corresponding lactam—7-aza-3α-hydroxy-5α-pregnane-6,20-dione—was inactive. [Display omitted]