Synthesis of Steroidal D‐Ring‐Fused Pyrrolidines of Dehydroepiandrosterone. Issue 25 (19th April 2017)

• Record Type: Journal Article
• Authors: Blanco‐Ania, Daniel; W. M. Aben, René; van Berkom, Leon W. A.; Scheeren, Hans W.; Rutjes, Floris P. J. T.
• Is Part Of: European journal of organic chemistry. Issue 25(2017)
• Page Start: 3729
• Page End: 3737
• Publication Date: 2017-04-19
• Subjects: Steroids -- Nitrogen heterocycles -- Cycloaddition -- High‐pressure chemistry -- Cascade reactions; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201601670
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : The commercially available steroid dehydroepiandrosterone 3‐acetate (DHEA) was converted into steroidalD ‐ring‐fused pyrrolidines that combine two privileged structures: a steroid and a (2‐arylethyl)amine. The three‐step transformations proceeded through conversion of the C‐17 ketone into an enol ether, followed by high‐pressure‐mediated cascade [4+2]/[3+2] cycloadditions with two nitroalkenes ([4+2]) and five dipolarophiles ([3+2]) to yield azonite intermediates. Finally, reduction of these azonites formed the new azasteroids, which are suitable for further derivatization. Abstract : Dehydroepiandrosterone 3‐acetate (DHEA) was transformed into functionalized azasteroids in three steps. These azasteroids contain a (2‐arylethyl)amine moiety contained within a pyrrolidine framework. The key step of these transformations was a high‐pressure‐promoted cascade [4+2]/[3+2] cycloaddition. The azasteroid products are suitable for combinatorial chemistry.