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High‐Pressure‐Mediated Extension of the Privileged Steroid Scaffold
Author(s) -
BlancoAnia Daniel,
Aben René W. M.,
van Berkom Leon W. A.,
Scheeren Hans W.,
Rutjes Floris P. J. T.
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201301511
Subject(s) - chemistry , cycloaddition , steric effects , alkene , steroid , surface modification , ring (chemistry) , diene , stereochemistry , combinatorial chemistry , medicinal chemistry , organic chemistry , catalysis , biochemistry , natural rubber , hormone
Abstract The commercially available steroid dehydroepiandrosterone 3‐acetate (DHEA) was converted into new, highly functionalized spiro derivatives by modification of the D‐ring. The transformation proceeded through conversion of the C‐17 carbonyl group into an electron‐deficient alkene, followed by either [2+2] or [4+2] cycloaddition. The cycloaddition reactions were successful for alkylidene malononitriles and 2‐cyano acrylates. Application of high pressure (15 kbar) was essential for good conversions due to the high steric hindrance on position C‐17. The cycloadducts formed from the reaction of 2‐cyano acrylates and Danishefsky's diene have high potential for further functionalization.