Synthesis of Spiro[cyclohexane-1,2′-[2H]indene] derivatives as inhibitors of steroid 5α-reductase

✍ Scribed by Shu-Kun Lin; Vittorio Rasetti

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: German
• Weight: 593 KB
• Volume: 78
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19950780407

✦ Synopsis

Abstract

The spiro[cyclohexane‐1,2′‐[2__H__]indene] derivatives 15a,b with molecular dimensions and nucleophilic functional groups similar to known steroid 5α‐reductase inhibitors (e.g. 2) were synthesized. The spiro[cyclohexane‐1,2′‐[2__H__]indene]‐1′(3′H),4‐dione (5) was synthesized from 5‐methoxyindan‐l‐one ( = 2,3‐dihydro‐5‐methoxy‐1__H__‐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.