17α-羟基-16β-甲基-5,9(11)-孕甾二烯-3,20-二缩酮的D环高碳化

D-Homoannulation of 17α-Hydroxy-16β-methyl-5, 9(11)-Pregnadienes-3, 2O-dione-bis (diethylene Ketal)

17α-羟基-16β-甲基-4,9（11）-孕甾二烯-3,20-二缩酮（1）经70％醋酸水解即得其相应的3,20-二酮化合物（2）,它是制备倍他美松（Betamethasone）的重要中间体。但1如用98％醋酸水解却不能得到2,而得重排产物3。据文献[1]报道:16β-甲基-17α-羟基-20-孕甾酮类具有很强的反应活性,容易发生D环高碳化。17α-羟基-20孕甾酮（4）在Lewis酸存在下,也发生重排生成D环高碳17a-酮（5）。5的17-羟基构型与4的相同。据此我们推测该重排产物可能是具有D环高碳的3,并经以下反应得到证明:2与BF3·Et2O在醋酐-醋酸中反应,

17α-hydroxy-16β-methyl-5, 9 (ll)-pregnadiene-3, 20-dione-bis (diethylene katal) (1) on treatment with 70% acetic acid was hydrolyzed to the parent 3, 20-dione, (2) in 88% yield, while compound 1 or 2 on treatment with 98% acetic acid was rearranged to 17α-hydroxy-16β, 17β-dimethyl-D-homo-4, 9(11)-androstandiene-3, 17a-dione (3) in 68 or 89% yield respectively. Compound 1 or 2 reacted with 70% acetic acid containing CaCl_2 to give 16β, 17aβ-dimethyl-D-homo-4, 9 (11), 15-androstatrien-3, 17-dione(7) in 90% yield. The yield of compound 7 is dependent on the concentration of CaCl_2 and the time of reaction.