High‐Pressure‐Mediated Extension of the Privileged Steroid Scaffold. Issue 7 (18th December 2013)

• Record Type: Journal Article
• Authors: Blanco‐Ania, Daniel; Aben, René W. M.; van Berkom, Leon W. A.; Scheeren, Hans W.; Rutjes, Floris P. J. T.
• Is Part Of: European journal of organic chemistry. Issue 7(2014)
• Page Start: 1438
• Page End: 1444
• Publication Date: 2013-12-18
• Subjects: Medicinal chemistry -- Natural products -- Steroids -- Spiro compounds -- High‐pressure chemistry -- Cycloaddition; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201301511
• Languages: English
• ISSNs: 1434-193X

Abstract

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. Abstract : In the quest for new biologically active steroid derivatives, dehydroepiandrosterone 3‐acetate (DHEA) was transformed into a highly functionalized spiro steroid in eight steps. The key step of this transformation involves a high‐pressure‐promoted Diels–Alder cycloaddition. The spiro steroid product is amenable for combinatorial chemistry.