Efficient synthesis of 1,4-thiazepanones and 1,4-thiazepanes as 3d fragments for screening libraries

Anil K Pandey, Steven E. Kirberger, Jorden A. Johnson, Jennifer R Kimbrough, Danika K.D. Partridge, William C.K. Pomerantz

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


1,4-Thiazepanes and 1,4-thiazepanones represent seven-membered ring systems with highly 3D character and are currently underrepresented in fragment screening libraries. A nuclear magnetic resonance (NMR) fragment screen identified 1,4-acylthiazepanes as new BET (bromodomain and extraterminal domain) bromodomain ligands; however, an efficient and readily diversified synthesis for library development has not been reported. Here we report a one-pot synthesis using α,β-unsaturated esters and 1,2-amino thiols to form 1,4-thiazepanones as precursors to 1,4-thiazepanes with high 3D character. This reaction proceeds in reasonable time (0.5-3 h) and in good yield and tolerates a broad scope of α,β-unsaturated esters. Several 1,4-thiazepanes were synthesized by a two-step transformation and were characterized as new BET bromodomain ligands using protein-observed 19F NMR. This synthesis should provide ready access to diverse 3D fragments for screening libraries.

Original languageEnglish (US)
Pages (from-to)3946-3950
Number of pages5
JournalOrganic Letters
Issue number10
StatePublished - May 15 2020

Bibliographical note

Funding Information:
We acknowledge the NIH Biotechnology training grant 5T32GM008347-23 and the Masonic Cancer Center for funding.

Publisher Copyright:
© 2020 American Chemical Society.


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