Synthesis of Spiro[cyclohexane-1,2′-[2H]indene] derivatives as inhibitors of steroid 5α-reductase |
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Authors: | Shu-Kun Lin Vittorio Rasetti |
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Abstract: | The spirocyclohexane-1,2′-2H]indene] derivatives 15a , b with molecular dimensions and nucleophilic functional groups similar to known steroid 5α-reductase inhibitors (e.g. 2 ) were synthesized. The spirocyclohexane-1,2′-2H]indene]-1′(3′H),4-dione ( 5 ) was synthesized from 5-methoxyindan-l-one ( = 2,3-dihydro-5-methoxy-1H-inden-1-one). A Grignard reaction and a dehydration step led to the cyclohexene (±)- 7 which, upon a stereoselective hydrogenation catalyzed by Raney-Ni under mild conditions, gave 8a as a pure epimer. Further hydrogenation and hydrogenolysis of 8a over Pd/C at room temperature reduced the keto group to give pure 9a . Finally, the 5′-substituted derivatives 12a , 14a , and 15a were generated by deprotection and Heck-type reaction. |
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