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Synthesis of Spiro[cyclohexane‐1,2′‐[2 H ]indene] derivatives as inhibitors of steroid 5α‐reductase
Author(s) -
Lin ShuKun,
Rasetti Vittorio
Publication year - 1995
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19950780407
Subject(s) - chemistry , indene , cyclohexane , raney nickel , hydrogenolysis , steroid , stereoselectivity , epimer , medicinal chemistry , cyclohexene , catalytic hydrogenation , stereochemistry , catalysis , organic chemistry , biochemistry , hormone
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.