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Formal Semisynthesis of Demethylgorgosterol Utilizing a Stereoselective Intermolecular Cyclopropanation Reaction
Author(s) -
Rosenbaum Nicolai,
Schmidt Lisa,
Mohr Florian,
Fuhr Olaf,
Nieger Martin,
Bräse Stefan
Publication year - 2021
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.202100035
Subject(s) - cyclopropanation , chemistry , semisynthesis , ketone , diastereomer , stereoselectivity , aldehyde , cyclopropane , total synthesis , yield (engineering) , stereochemistry , swern oxidation , carbenoid , wittig reaction , organic chemistry , catalysis , rhodium , ring (chemistry) , materials science , dimethyl sulfoxide , metallurgy
In this study, we report a convenient and high yielding formal semisynthesis of demethylgorgosterol, a marine steroid with an intriguing sidechain containing a cyclopropane unit. This was achieved through the synthesis of an advanced ketone intermediate. The synthetic route features a total of ten steps, starting from commercially available stigmasterol, with an overall yield of 27 %. The key step was a stereoselective intermolecular cyclopropanation reaction. This reaction proceeded in 82 % yield, the resulting cyclopropane carboxylic ester shows a trans/cis ratio of 89 : 11, with a diastereomeric ratio for the trans‐diastereomers of >99 : 1. A reduction/oxidation sequence afforded the corresponding aldehyde, which was used in a Grignard reaction. A final oxidation step then yielded the desired ketone. This novel route presents a platform to further investigate the medicinal applications of gorgosterol‐type steroids and to fully understand their role in coral symbiosis.