| Steroidal 3,5-dienes are a kind of bioactive steroids that can be used as aromatase inhibitors for the treatment of breast cancer.Besides,steroidal 3,5-dienes also possess the activity for interruption of early pregnancy and can be also used as selective estrogen receptor modulators.At the same time,steroidal 3,5-dienes serve as not only key structural motifs,but also important synthetic precursors of a variety of bioactive structures.However,there lacks a satisfactory and easy operated method to produce a diverse range of pharmaceutically important steroidal 3,5-dienes.In this thesis,a new method to prepare steroidal 3,5-dienes via reduction-elimination of steroidal 4-en-3-ones in water has been developed.In the presence of recently developed iridium catalysts(0.5 mol%,S/C=200),by simply heating steroidal 4-en-3-ones in a water-cosolvent with formic acid at 80? for several hours,steroidal 3,5-dienes are obtained in moderate to excellent yields.Mechanistic studies indicate that the process consists of two consecutive reactions:iridium-catalyzed selective reduction of 4-en-3-ones to 4-en-3-ols and acid-promoted selective dehydration of 4-en-3-ols to 3,5-dienes.The reaction conditions are mild in water without inert atmosphere protection.The reduction-elimination shows extremely high functionality tolerance.Primary,secondary and tertiary hydroxyl groups are well tolerated.Neither hydrolysis nor reduction is observed when steroidal esters(except for formates)or tolylates are used under the acidic reductive conditions.Surprisingly,the endocyclic or exocyclic ketone moieties are not affected.In addition,our method also features excellent regioselectivity.The reduction-elimination only takes place at A-ring 4-en-3-ones,while B-or C-ring enones are unreactive.This method can be also used to synthesize bicyclic conjugated dienes,and the product 3,5-dienes can be also used to synthesize steroids with biological activity. |
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