Steroid structure and function V. A-ring conformation in 17-hydroxy-6α-methylprogesterone

The molecular conformation of 17-hydroxy-6α-methylprogesterone has been determined crystallographically and is compared with 17-hydroxy-progesterone, 17-acetoxyprogesterone and 17-acetoxy-6α-methylprogesterone (MPA). The analysis demonstrates that the 6α-methyl substituent is not sufficient by itself to induce inversion of the A-ring. Consequently, the inverted form observed in MPA and proposed to be responsible for high affinity binding to the progesterone receptor appears to be induced by the combined long range influence of 17α-acetoxy substituent and the direct interaction of the 6α-methyl group with the flexible A-ring.